CA3168784A1 - Inactivated sars-cov-2 virus vaccine - Google Patents

Inactivated sars-cov-2 virus vaccine Download PDF

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CA3168784A1
CA3168784A1 CA3168784A CA3168784A CA3168784A1 CA 3168784 A1 CA3168784 A1 CA 3168784A1 CA 3168784 A CA3168784 A CA 3168784A CA 3168784 A CA3168784 A CA 3168784A CA 3168784 A1 CA3168784 A1 CA 3168784A1
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sars
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Andreas Meinke
Michael Mohlen
Robert Schlegl
Jurgen Heindl-Wruss
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Valneva Austria GmbH
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    • AHUMAN NECESSITIES
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • AHUMAN NECESSITIES
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    • AHUMAN NECESSITIES
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    • A61K2039/5252Virus inactivated (killed)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K39/00Medicinal preparations containing antigens or antibodies
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    • A61K2039/55505Inorganic adjuvants
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    • C12N2770/20011Coronaviridae
    • C12N2770/20034Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
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    • C12N2770/00MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011Details
    • C12N2770/20011Coronaviridae
    • C12N2770/20061Methods of inactivation or attenuation
    • C12N2770/20063Methods of inactivation or attenuation by chemical treatment

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Abstract

Described herein are SARS-CoV-2 vaccines and compositions and methods of producing and administering said vaccines to subjects in need thereof.

Description

INACTIVATED SARS-CoV-2 VIRUS VACCINE
FIELD OF THE INVENTION
The disclosure relates to SARS-CoV-2 vaccines and compositions and methods for producing said vaccines and administering the vaccines to subjects for the generation of an anti -SARS-CoV-2 immune response.
BACKGROUND OF THE INVENTION
SARS-CoV-2 (hereinafter the -virus") was detected for the first time in China around November 2019. Since then, the virus has caused a global pandemic. The natural reservoir are bats and the virus belongs to the Coronaviridae family, genus Betacoronavirus (betaCoV). The virus has a ssRNA
genome. 29.903 bp (Wuhan-Hu-1: GenBank Reference sequence: NC_045512.2) encoding for 9,860 amino acids, 25 non-structural protein and 4 structural proteins: spike (S), envelope (E), membrane (M), nucleocapside (N). The virus has a variable size of between 60 to 140 nm in diameter. It is enveloped and sensitive to UV, heat, and lipid solvents. It has 89% nucleotide identity with bat SARS-like-CoVZXC21 and 81% nucleotide identity with human SARS-CoV. Evidence suggests that this virus spreads when an infected person coughs small droplets - packed with the virus - into the air. These can be breathed in, or cause an infection if one touches a surface they have landed on, then one's eyes, nose or mouth. In addition, other vectors may exist, and the virus may be transmitted by blood transfusion, transplacentally, and through sexual transmission. Though the symptoms of SARS-CoV-2 virus infection may be mild, and include typically fever and cough, it can also be asymptomatic or in the other extreme fatal. The key symptoms are usually high temperature, cough and breathing difficulties. There is currently no specific treatment or vaccine for this virus, and the only preventative methods involve social distancing. SARS-CoV-2 presents a substantial public health threat. The Imperial College COVID-19 (disease caused by SARS-CoV-2) Response Team published in March 16, 2020 a report wherein they evaluated all possible methods to stop or delay the spread of the virus leading ultimately to the break-down of the healthcare system and hundreds of thousands of deaths in the UK alone. They stated that only population-wide social distancing has a chance to reduce effects to manageable levels. These measures need to be upheld until a vaccine is available. This recommendation would mean for most of the population quarantine for at least 18 months. They concluded that a mass-producible vaccine is the only option to stop this pandemic other than willing to sacrifice the elderly population. In view of the dramatic situation, there is an absolute urgent need for an effective vaccine against SARS-CoV-2 as fast as possible.
Furthermore, various escape mutants have emerged (e.g. UK_B.1.1.7; South African B.1.351;
Brazilian_P.1 variants, and Californian variants B.1.427 and B.1.429; see also figure 2) which further worsen the situation and thus this unfortunate development needs to be addressed as well.

SUMMARY OF 'THE INVENTION
Accordingly, the present invention provides an inactivated SARS-CoV-2 vaccine.
Whilst extensive effort has already been invested by research groups throughout the world in developing a SARS-CoV-
2 vaccine, most approaches have focused on subunit vaccines (e.g. encoding the SARS-CoV-2 S protein or fragments thereof), live attenuated vaccines or recombinant DNA or RNA
vaccines encoding viral proteins. However, there has been little interest in whole virus, inactivated vaccine approaches, and a successful inactivated SARS-CoV-2 vaccine has not yet been fully developed. In so far as an inactivated vaccine approach has been contemplated, the use of typical inactivating agents (e.g.
formaldehyde) and adjuvants (e.g. alum) under standard conditions may have drawbacks which hinder development of an effective vaccine candidate. Moreover, there is a risk that such a vaccine candidate could result in antibody-dependent enhancement (ADE) of SARS-CoV-2 disease and/or Th2 type immunopathology possibly resulting from the hypersensitivity responses to SARS-CoV-2 components.
The present invention aims to address these problems and thus to produce a safe and effective whole virus, inactivated SARS-CoV-2 vaccine that overcomes the drawbacks of the prior art.
Thus in one aspect the present invention provides a SARS-CoV-2 vaccine comprising a beta-propiolactone-inactivated SARS-CoV-2 particle; wherein the vaccine is capable of generating neutralizing antibodies against native SARS-CoV-2 particles in a human subject. Preferably a native surface conformation of the SARS-CoV-2 particle is preserved in the vaccine.
In another aspect the present invention provides a SARS-CoV-2 vaccine comprising an inactivated SARS-CoV-2 particle; wherein a native surface conformation of the SARS-CoV-2 particle is preserved in the vaccine, such that the vaccine is capable of generating neutralizing antibodies against native SARS-CoV-2 particles and/or other immunological responses in a human subject that are able to protect partly or fully more than 50%, preferably more than 60%, more than 70%, more than 80%, more than 90% of said vaccinated human subjects.
In particular, the present invention aims to provide optimally inactivated SARS-CoV-2 particles, which are incapable of replication and infection of human cells, but which retain immunogenic epitopes of viral surface proteins and are thus suitable for generating protective immunity in vaccinated subjects.
By optimizing the inactivation process and other steps in the production of the vaccine, including the selection of an appropriate adjuvant, a novel vaccine composition can be obtained that preserves a native surface conformation of SARS-CoV-2 particles and which reduces the risk of negative effects such as ADE and immunopathology. Such vaccine compositions are described in more detail below.

In a further particular embodiment, the invention aims to provide an optimal combination of optimally inactivated different SARS-CoV-2 particles, which are incapable of replication and infection of human cells, but which retain immunogenic epitopes of viral surface proteins and are thus suitable for generating protective immunity in vaccinated subjects. By an optimal combination of different and optimally inactivated SARS-CoV-2 particles, an improved vaccine composition can be obtained that is capable of generating neutralizing antibodies against native SARS-CoV-2 particles and/or other immunological responses in a human subject that are able to protect partly or fully more than 50%, preferably more than 60%, more than 70%, more than 80%, more than 90% of said vaccinated human subjects.
Each of the limitations of the invention can encompass various embodiments of the invention. It is therefore anticipatcd that each of thc limitations of the invention involving any one clement or combinations of elements can be included in each aspect of the invention. This invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways.
BRIEF DESCRIPTION OF THE DRAWINGS
The accompanying drawings are not intended to be drawn to scale. The figures are illustrative only and are not required for enablement of the disclosure. For purposes of clarity, not every component may be labeled in every drawing. In the drawings:
Figure 1. The process for production of the inactivated SARS-CoV-2 vaccine of the current invention.
Steps include cell buildup of Vero host cells, infection of Vero cells with SARS-CoV-2, virus harvest.
DNA reduction, primary inactivation, purification, optional secondary inactivation and formulation with adjuvant.
Figure 2. During the course of the SARS-CoV-2 pandemic, SARS-CoV-2 genomic sequences from isolates from around the world have been reported including the recent new variants or lineages such as the UK B 1.1.7, Brazilian Pl, Californian B.1.427/B.1.429 and South African B.1.351 lineages. The accession numbers and origins of complete SARS-CoV-2 genomic sequences are provided in tabular form, along with accession numbers for the corresponding orflab polyprotein and S protein, when available (- or no entry = not available).
3 Figure 3. A preferred set-up for the sucrose gradient centrifugation used as a polishing step for the SARS-CoV-2 vaccine of the invention.
Figure 4. Total IgG in response to SARS-CoV-2 vaccine. Coating antigens: Si (A), receptor binding domain of spike protein (B) and nucleoprotein (C). Endpoint titer: absorbance of 3-fold the blank used as cut-off (dashed line).
Figure 5. lgG1 and 1gG2a titers in response to SARS-CoV-2 vaccine adjuvanted with alum. Antibody titers specific to Si protein were determined by ELISA. The concentrations were determined by comparison with a mAb subclass standard curve.
Figure 6. Production process delivers high density and intact spike proteins.
Shown are electron micrographs of the SARS-CoV-2 inactivated drug substance produced according to Example 1. About 1-1.5 107 viral particles per AU.
Figure 7. Comparison of Size-Exclusion-Chromatography and SDS-PAGE profiles of SARS-CoV-2 and JEV drug substance. High purity (>95%) according to SDS-PAGE (silver stain, reduced) and monomer virus (>95%) according to SE-HPLC. Difference in retention time due to different virus particle size (JEV (IXIARO) about 50nm, SARS-CoV2 about 100nm) Figure 8. Study design for NHP challenge study. Three groups of 8 animals each; Two dose groups for SARS-CoV-2 vaccine (10 AU & 40 AU, formulated with 0.5 mg/dose AP+ and 1 mg Thl-stimulating adjuvant per dose added directly before administration) and a placebo group (DPBS). The SARS-CoV-2 challenge strain is BetaCoV/France/IDF/0372/2020 (Maisonmasse et al., Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates, 2020, Nature 585:584-587).
Methods and timing of testing: Hematology on d-28, dO, d7, d14, d21, d28, d35, d47, d49, d50, d51, d54, d62. Ab response (ELISA, IFA) on d-28, dO, d14, d21, d28, d35, d47, d54, d62. T cell response (ICS. ELISPOT) on d-28, dO, d14, d35, d54, d62. Cytokine response (LUMINEX) on d47, d49, d50, d51, d54, d62.
SWABS (viral load (qRT-PCR-genomic + subgenomic): nasal & tracheal swabs on d35, d49, d50, d51, d54, d57, d62; rectal swabs at baseline and on d2, d7, d15. BAL viral load (qRT-PCR-genomic +
subgenomic): d50. Euthanasia: lung harvest, viral load (qRT-PCR - genomic +
subgenomic): d54, d62.
CT scans: d35, d50, d57.
Figure 9. Counts of residues within the footprints of 33 neutralizing mAbs, or respectively clusters 13,
4, 10, 2, 1, 3. Listed are residues within the footprint of neutralizing mAbs and/or which are lineage
5 defining mutation positions for B.1.1.7, B.1.351 or P.1 (marked "x"). E.g.
K417 and E484 mutations which are amino acid positions in the S-protein are only to be found in the South African and Brazilian lineages.
Figure 10. SDS-PAGE, silver stain, of two samples of SARS-CoV-2 candidates according to Example 1 (iCELLIS 500 bioreactor, protamine sulfate precipitated, BPL inactivated).
The bands could be clearly attributed to the three main viral proteins (Spike-protein, Membrane-protein, Nucleoprotein) as well as to background proteins from the host system.
Figure 11. SARS-CoV-2 Mutations within the Spike Protein of strain UK MIG457 (B.1.1.7 lineage) and strain SA_P2 (B.1.351 lineage) from Public Health England (PHE).
DETAILED DESCRIPTION OF THE INVENTION
Embodiments of the present invention are directed to a SARS-CoV-2 vaccine or immunogenic composition comprising inactivated SARS-CoV-2 particles. Typically, the inactivated SARS-CoV-2 particles are whole virus, inactivated particles, i.e. the inactivated virus particles are derived from whole native SARS-CoV-2 particles that have been inactivated. As used herein "SARS-CoV-2" refers to the SARS-CoV-2 virus and "SARS-CoV-2 particles" typically refers to whole SARS-CoV-2 viral particles, i.e. virions.
In some embodiments of the present invention, the SARS-CoV-2 particles are inactivated without substantially modifying their surface structure. In other words, a native surface conformation of the SARS-CoV-2 particles is retained in the inactivated virus particles. It has surprisingly been found that by optimizing an inactivation process, e.g. using beta-propiolactone, infectivity of native SARS-CoV-2 particles can be substantially abrogated without adversely affecting their antigenicity and/or immunogenicity. Thus, the present invention provides in one aspect an inactivated virus vaccine (e.g.
a beta-propiolactone-inactivated virus vaccine) that generates neutralizing antibodies and/or protective immunity against SARS-CoV-2 infection.
In one embodiment, the SARS-CoV-2 particles are inactivated by a method that preferentially targets viral RNA. By this it is meant that e.g. the inactivation step modifies viral RNA more than viral proteins. Thus, the inactivated SARS-CoV-2 particles may comprise replication-deficient viral RNA, i.e. the viral RNA is modified in the inactivation step such that the inactivated particles are incapable of replicating. By utilizing an inactivation method that preferentially targets viral RNA, the present invention advantageously allows the preservation of immunogenic epitopes in viral surface proteins.
Preferably, the inactivation method spares viral (surface) proteins relative to viral RNA, e.g. the viral surface proteins (e.g. the spike (S) protein) may comprise fewer or more infrequent modifications resulting from the inactivation step compared to viral RNA. For instance, a lower proportion of amino acid residues in the viral surface proteins (e.g. S protein) may be modified by the inactivation step compared to the proportion of modified nucleotide residues in the viral RNA.
In some embodiments, the proportion of modified amino acid residues in the viral surface proteins (e.g. S protein) may be at least 5%, 10%, 20%, 30%, 50%, 70% or 90% lower than the proportion of modified nucleotide residues in the viral RNA. By "modifications" or "modified residues" it is meant to refer to non-native residues that are not present in the native SARS-CoV-2 particles, e.g. chemical (covalent) modifications of such residues resulting from the inactivation step.
In one embodiment, the viral RNA is inactivated by alkylation and/or acylation, i.e. the modifications in the SARS-CoV-2 inactivated particles comprise alkylated and/or acylated nucleotide residues. In some embodiments, the modifications are preferentially targeted to purine (especially guanine) residues, e.g. the SARS-CoV-2 inactivated particles comprise one or more modified (e.g. alkylated or acylated) guanine residues. In some cases, the inactivation step may lead to cross-linking of viral RNA
with viral proteins, e.g. via guanine residues in the viral RNA. The inactivation step may also introduce nicks or strand breaks into viral RNA, e.g. resulting in fragmentation of the viral genome.
Suitable alkylating and/or acylating agents are known in the art. In one embodiment, the inactivating agent comprises beta-propiolactone, i.e. the vaccine comprises beta-propiolactone-inactivated virus particles. In any case, in a particular embodiment, beta-propiolactone (herein referred to also as -BPL") treatment is particularly preferred according to the present invention, because it results in SARS-CoV-2 particles, that are substantially inactive, but which retain high antigenicity and immunogenicity against neutralizing epitopes present in native SARS-CoV-2. In particular, it has been surprisingly found that beta-propiolactone can be used to inactivate SARS-CoV-2 particles with a minimum number of protein modifications. For instance, as demonstrated in Examples 6 and 7 below, inactivation of SARS-CoV-2 particles using beta-propiolactone results in a much lower number of modifications of viral proteins compared to inactivation of influenza particles by beta-propiolactone. Thus in beta-propiolactone-inactivated SARS-CoV-2 particles, a native surface conformation of the viral particles can be preserved.
6 In a preferred embodiment of the invention, the viral RNA is inactivated in an optimized manner, i.e.
such it is just sufficiently inactivated not to be infectious anymore but not "over"-inactivated so that numerous modification at different amino acids in particular at the S-protein occur. In a further even more preferred embodiment, the BPL inactivation not only sufficiently inactivates (but not over-inactivates) the SARS-CoV-2 virus but also just sufficiently inactivates viruses that might be co-enriched and co-cultured in the manufacturing process (see e.g. experimental part). A particularly hard virus to inactivate that can co-culture and be co-enriched is PPV (porcine parvovirus) ยจ see experimental part.
The concentration of beta-propiolactone in the inactivation step may be optimized to ensure complete inhibition of viral replication whilst preserving the conformation of surface proteins in the virus. For instance, the concentration of beta-propiolactone in the inactivation step may be e.g. 0.01 to 1% by weight, preferably 0.01 to 0.1% by weight, more preferably about 0.03% by weight. A preferred amount of BPL was found to be 500ppm where the SARS-CoV-2 virus but also other concerning viruses/impurities are inactivated whilst preserving (i.e. not modifying) most of the amino acids of the S-protein (i.e. only a few amino acids were shown to be modified at low probability).
In some embodiments, the native SARS-CoV-2 particles may be contacted with beta-propiolactone for at least 5 hours, at least 10 hours, at least 24 hours or at least 4 days, e.g. 5 to 24 hours or longer such as 48 hours. The inactivation step may be performed at about 0 C to about 25 C, preferably about 4 C
or about 22 C, or e.g. 18 to 24 C. In one embodiment the inactivation step (e.g. with beta-propiolactone) is performed at 2 C to 8 C for 24 hours. The inactivation step may optionally and preferably be followed by a hydrolyzation step of the inactivating agent, as is known in the art (which may be performed e.g. at about 37 C+/- 2 C for a total time of 2.5 hours +/-0.5 hours for beta-propiolactone). Typically, longer incubation times and/or higher temperatures in the inactivation step may enhance viral inactivation, but may also lead to an increased risk of undesirable surface modifications of the viral particles, leading to reduced immunogenicity.
Therefore, the inactivation step may be performed for e.g. the shortest time necessary in order to produce a fully inactivated virus particle. After completion of the hydrolysis, the inactivated viral solution was in one embodiment immediately cooled down to 5+3 C and stored there until inactivation was confirmed by large volume plaque assay and serial passaging assay.
Beta-propiolactone inactivation of SARS-CoV-2 particles may preferentially modify cysteine, methionine and/or histidine residues. Thus in some embodiments, the inactivated SARS-CoV-2 particle comprises one or more beta-propiolactone-modified cysteine, methionine and/or histidine residues.
7 However, in embodiments of the present invention, the beta-propiolactone-inactivated SARS-CoV-2 particles show relatively few protein modifications. Thus, for example, an inactivated SARS-CoV-2 particle in the vaccine may comprise fewer than 200, 100, 50, 30, 20, 15, 10, 9, 8, 7 or 6 beta-propiolactone-modified amino acid residues. Preferably a spike (S) protein of the inactivated SARS-CoV-2 particle comprises fewer than 100, 50, 30, 20, 15, 10, 9, 8, 7 or 6 beta-propiolactone-modified amino acid residues. More preferably the inactivated SARS-CoV-2 particle or spike protein thereof comprises 20 or fewer, 15 or fewer, 10 or fewer, or 5 or fewer beta-propiolactone-modified amino acid residues. Most preferably the inactivated SARS-CoV-2 particle or spike protein thereof comprises 1 to 100, 2 to 70, 3 to 50, 4 to 30, 5 to 25, 5 to 20, 10 to 20 or about 15 beta-propiolactone-modified amino acid residues.
In another embodiment, fewer than 20%, 15%, 10%, 5% or 4% of SARS-CoV-2 polypeptides are beta-propiolactonc-modificd. For instance, 0.1 to 10%, 1 to 8%, 2 to 7% or about 3%, 4%, 5% or 6% of SARS-CoV-2 polypeptides in the particle may be beta-propiolactone-modified.
Beta-propiolactone modification of residues and/or polypeptides in the vaccine may be detected by mass spectrometry, e.g.
using liquid chromatography with tandem mass spectrometry (LC-MS-MS), for instance using a method as described in Examples 6 and 7. In such a method, the SARS-CoV-2 particles may be digested in order to fragment proteins into SARS-CoV-2 polypeptides for LC-MS-MS
analysis. The digestion step may be performed by any suitable enzyme or combination of enzymes, e.g.
by trypsin, chymotrypsin and/or PNGase F (peptide:N-glycosidase F), or by e.g. acid hydrolysis. Preferably the percentage of BPL-modified polypeptides detected by LC-MS-MS following enzymatic digestion or acid hydrolysis is: (a) trypsin digestion, 1 to 5%, 2 to 4% or about 3%; (b) trypsin + PNGase F digestion, 1 to 5%, 2 to 4% or about 3%; (c) chymotrypsin, 1 to 10%, 3 to 8% or about 6%;
(d) acid hydrolysis, 1 to 6%, 2 to 5% or about 4%. In this context, a "beta-propiolactone-modified"
polypeptide means that the polypeptide comprises at least one beta-propiolactone modification, e.g.
at least one beta-propiolactone-modified residue.
In some embodiments, a spike (S) protein of the inactivated SARS-CoV-2 particle comprises a beta-propiolactone modification at one or more of the following residues: 49, 146, 166, 177, 207, 245, 379, 432, 519, 625, 1029, 1032, 1058, 1083, 1088, 1101, 1159 and/or 1271, e.g. in SEQ ID NO: 3, or a corresponding position in SEQ ID NO: 19, 21, 23, 25 or 27. Preferably the inactivated SARS-CoV-2 particle comprises a beta-propiolactone modification at one or more of the following residues: H49, H146, C166, M177, H207, H245, C432, H519, H625, M1029, H1058, H1083, H1088, H1101, H1159 and/or H1271, e.g. in SEQ ID NO: 3, or a corresponding position in SEQ ID NO:
19, 21, 23, 25 or 27.
In another embodiment, the inactivated SARS-CoV-2 particle comprises a beta-propiolactone
8 modification at one or more of the following residues: H207, H245, C379, M1029 and/or C1032, e.g.
in SEQ ID NO: 3, or a corresponding position in SEQ ID NO: 19, 21, 23, 25 or 27. By "a corresponding position" it is meant a position in SEQ ID NO: 19, 21, 23, 25 or 27 that aligns with position H207, H245, C379, M1029 and/or C1032 in SEQ ID NO: 3, e.g. when SEQ ID NO: 19, 21, 23, 25 or 27 is aligned with SEQ ID NO:3 using a program such as NCBI Basic Local Alignment Search Tool (BLAST).
For instance, in some embodiments, the positions in SEQ ID NO: 19, 21, 23, 25 or 27 corresponding to H207, H245, C379, M1029 and C1032 in SEQ ID NO: 3 are shown below:
Scq ID

In some embodiments, a membrane (M) glycoprotein of the inactivated SARS-CoV-2 particle comprises a beta-propiolactone modification at one or more of the following residues: 125, 154, 155, 159 and/or 210, preferably 1-1154, H155, C159 and/or H210, e.g. in SEQ ID NO:
29.
In some embodiments, a nucleocapsid (N) protein of the inactivated SARS-CoV-2 particle comprises a beta-propiolactone modification at M234, e.g. in SEQ ID NO: 28.
In some embodiments, fewer than 30%, 20%, 10%, 5%, 3% or 1% of one or more of the following residues in the inactivated SARS-CoV-2 particles are beta-propiolactone modified: (i) in the spike (S) protein, e.g. in SEQ ID NO: 3, or a corresponding position in SEQ ID NO: 19, 21, 23, 25 or 27: residues 49, 146, 166, 177, 207, 245, 379, 432, 519, 625, 1029, 1032, 1058, 1083, 1088, 1101, 1159 and/or 1271, preferably H49, H146, C166, M177, H207, H245, C432, H519, H625, M1029, H1058, H1083, H1088, H1101, H1159 and/or H1271; alternatively H207, H245, C379, M1029 and/or C1032;
(ii) in the membrane (M) glycoprotein, e.g. in SEQ ID NO: 29: residues 125, 154, 155, 159 and/or 210; preferably H154, H155, C159 and/or H210; and/or (iii) M234 of the nucleocapsid (N) protein, e.g. in SEQ ID NO:
28. In preferred embodiments, fewer than 30%, 20%, 10%, 5%, 3% or 1% of at least 2, 3, 4, 5, 6, 7, 8,
9 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19,20 or each of the above residues in the inactivated SARS-CoV-2 particles are beta-propiolactone modified. In this paragraph, the percentage of modified residues is intended to refer to the site occupancy, e.g. the ratio of modified to unmodified peptide for the same modification site normalized to the protein abundance as described in Examples 6 and/or 7 below.
In another preferred embodiment, the proportion of beta-propiolactone-modified residues (i.e. site occupancy) at the following positions in the inactivated SARS-CoV-2 particles is:
(i) in the spike (S) protein (e.g. of SEQ ID NO: 3, or a corresponding position in SEQ ID NO: 19, 21, 23,25 or 27):
(a) H207: less than 30%, preferably 0.01 to 25%; and/or (b) H245: less than 10%, preferably 0.1 to 5%; and/or (c) C379: less than 5%, less than 1% or less than 0.1%; and/or (d) M1029: less than 5%, less than 1% or less than 0.1%; and/or (e) C1032: less than 5%, less than 1% or less than 0.1%; and/or (ii) in the membrane (M) glycoprotein (e.g. of SEQ ID NO: 29):
(0H154: less than 5%, less than 1% or less than 0.1%; and/or (g) H155: less than 10%, preferably 0.1 to 5%; and/or (h) C159: less than 5%, less than 1% or less than 0.1%; and/or (i) H210: less than 20%, preferably 0.1 to 10%; and/or (iii) in the nucleocapsid (N) protein (e.g. of SEQ ID NO: 28):
(j) M234: less than 90%; less than 10% or less than 0.1%.
In another preferred embodiment, the proportion of beta-propiolactone-modified residues (i.e. site occupancy) at each of the following positions in the spike (S) protein (e.g.
of SEQ ID NO: 3, or a corresponding position in SEQ ID NO: 19, 21, 23, 25 or 27) of the inactivated SARS-CoV-2 particles is:
(a) residues H49, H146; C166, H207, H519, M1029, H1083, H1088, H1101, H1159 and/or H1271: less than 20%, preferably 0.01 to 10%, more preferably 0.1 to 5%;
and/or (b) residues M177, C432, H625: less than 30%, preferably 0.1 to 20%, more preferably 1 to
10%; and/or (c) residues H245, H1058: less than 30%, preferably 0.1 to 20%, more preferably 5 to 15%;
In some embodiments, the proportion of beta-propiolactone-modified amino acid residues in the inactivated SARS-CoV-2 particle (or spike (S) protein thereof) may be at least 5%, 10%, 20%, 30%, 50%, 70% or 90% lower than the proportion of modified residues in a beta-propiolactone-inactivated influenza particle (or hemagglutinin (HA) or neuraminidase (NA) protein thereof), e.g. in an influenza particle that has been inactivated under similar conditions to the SARS-CoV-2 particle.
In an alternative embodiment, the viral RNA may be inactivated by treatment with ultraviolet (UV) light. UV treatment can be used to preferentially target RNA (compared to polypeptides) in the viral particles, resulting in e.g. modified nucleotides and/or fragmentation. In some embodiments, UV
treatment can be combined with beta-propiolactone treatment to improve inactivation of the virus, e.g.
a beta-propiolactone treatment step can be followed by a UV treatment step or vice versa, or a UV
treatment step can be performed at the same time as the beta-propiolactone treatment step.
In other embodiments, the native SARS-CoV-2 particles may be inactivated using formaldehyde.
However, formaldehyde inactivation is typically less preferred in the present invention, as it is less suitable for preferentially targeting viral RNA and preserving immunogenic cpitopcs in the viral surface proteins.
Therefore in preferred embodiments, the inactivation step(s) (especially when using formaldehyde, but also when using other inactivating agents such as e.g. beta-propiolactone) are performed under mild conditions in order to preserve surface antigen integrity, especially integrity of the S protein.
In one embodiment, such a mild inactivation method comprises contacting a liquid composition comprising native SARS-CoV-2 particles with a chemical viral inactivating agent (such as e.g. any of the chemical inactivation agents as listed above or a combination, for instance formaldehyde or preferably beta-propiolactone) in a container, mixing the chemical viral inactivating agent and the liquid composition comprising SARS-CoV-2 particles under conditions of laminar flow but not turbulent flow, and incubating the chemical viral inactivating agent and the liquid composition comprising SARS-CoV-2 particles for a time sufficient to inactivate the viral particles. The mild inactivation step is optionally performed in a flexible bioreactor bag. The mild inactivation step preferably comprises 5 or less container inversions during the period of inactivation. Preferably, the mixing of the chemical viral inactivating agent and the composition comprising native SARS-CoV-2 particles comprises subjecting the container to rocking, rotation, orbital shaking, or oscillation for not more than 10 minutes at not more than 10 rpm during the period of incubation.
Suitable mild or gentle inactivation methods are described below in the Examples. Further details of such methods are also described inWO 2021/048221, the contents of which are incorporated herein in their entirety.
11 Typically, the inactivation step substantially eliminates infectivity of mammalian (e.g. human) cells by the inactivated SARS-CoV-2 particle. For instance, infectivity of mammalian cells may be reduced by at least 99%, 99.99% or 99.9999% as compared to a native SARS-CoV-2 particle, or infectivity of human cells by the inactivated A SARS-CoV-2 particle may be undetectable.
Standard assays may be used for determining residual infectivity and effective viral titer, e.g.
plaque assays, determination of TCID50 (50% tissue culture infectious dose). For instance, the mammalian cells may be MDCK, COS
or Vero cells.
In preferred embodiments of the present invention, a native surface conformation of the SARS-CoV-2 particles is preserved in the inactivated virus particles. By this it is meant that e.g. one or more or all immunogenic (neutralizing) epitopes are retained in the inactivated virus particles, such that the inactivated particles arc capable of generating neutralizing antibodies against native SARS-CoV-2 particles when administered to a human subject. By "native surface conformation" it is meant to refer to the surface conformation found in native SARS-CoV-2 particles, i.e. SARS-CoV-2 particles (virions) that have not been inactivated. The property of the vaccine or inactivated SARS-CoV-2 particles in generating neutralizing antibodies in a subject may be determined using e.g. a plaque reduction neutralization test (PRNT assay), e.g. using a serum sample from the subject as known in the art.
In preferred embodiments, the present invention comprises that a native conformation of (i) spike (S) protein; (ii) nucleocapsid (N) protein; (iii) membrane (M) glycoprotein;
and/or (iv) envelope (E) protein is preserved in the inactivated viral particles. Preferably, the inactivated SARS-CoV-2 particle comprises a native conformation spike (S) protein. Thus, the S (and/or N
and/or M and/or E) protein in the inactivated SARS-CoV-2 particle preferably comprises one or more or all (intact) immunogenic (neutralizing) epitopes present in native SARS-CoV-2 particles. Preferably, the S (and/or N and/or M
and/or E) protein in the inactivated viral particles is not modified, or not substantially modified by the inactivation step.
Preservation of the surface conformation of the viral particles can be assessed using standard techniques.
For instance, methods such as X-ray crystallography, MS analysis (shift of amino acid mass by modification) and cryo-electron microscopy may be used to visualize the virus surface. The secondary and tertiary structures of proteins present on the surface of viral particles may also be analyzed by methods such as by circular dichroism (CD) spectroscopy (e.g. in the far (190-250 nm) UV or near (250-300 nm) UV range). Moreover, preservation of a native surface conformation can be confirmed by using antibodies directed against epitopes present on the native viral surface, e.g. in the S protein.
12 Cross-reaction of anti-SARS-CoV-2 antibodies between the inactivated and native virus particles can thus be used to demonstrate retention of potentially neutralizing epitopes in the vaccine.
The surface conformation of SARS-CoV-2 virions and in particular the spike (S) protein is known, and has been published in several recent studies. See for instance Shang, J. et al. (Structural basis of receptor recognition by SARS-CoV-2. Nature https://doi.org/10.1038/s41586-020-2179-y (2020)), which describes the crystal structure of the SARS-CoV-2 receptor binding domain. In addition, Walls et al.
(Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein, Cell 180, 1-12 (2020), hups://doi.org/10.1016/j.ce11.2020.02.058) provides a detailed description of the S protein surface conformation using cryo-EM, and describes cross-neutralizing antibodies that target conserved S
protein epitopes. The use of antibodies from sera of infected and convalescent patients has shed further light on important S protein epitopes (Zhang B et al. Mining of epitopes on spike protein of SARS-CoV-2 from COVID-19 patients. 2020 Cell Research 30:702-704). Recent studies have also focused on the structure of the SARS-CoV-2 nucleocaspid (N) protein, which has been confirmed as an important antigen in studies using convalescent sera (Zeng W et al. Biochemical characterization of SARS-CoV-2 nucleocapsid protein. 2020 BBRC 527(3): 618-623). Further guidance with regard to potentially important SARS-CoV-2 epitopes is available in the COVIEdb database, a compilation of information from coronavinis epitope mapping studies (frUp://biopharm.zju.edu.cn/coyiedbi;
Wu J COVIEdb: A
Database for Potential Immune Epitopes of Coronaviruses. 2020 Front.
Phannacol. 11:572249; doi:
10.3389/fphar.2020.572249).
Monoclonal antibodies against SARS-CoV-2 surface epitopes (including in the S
protein) are described in the literature (e.g. as mentioned above), available from commercial sources and/or can be generated using standard techniques, such as immunization of experimental animals. For example, as of September 9, 2020, at least 169 different antibodies against SARS-CoV-2 were available from MyBioSource, Inc., San Diego, CA (e.g. cat. no. MB58574747, see www.MyBioSource.com). On the same date at least 28 different antibodies against SARS-CoV-2 were available from Sino Biological US
Inc., Wayne, PA (e.g. cat. no. 40150-D006, see https://www.sinobiologicatcomi). Further suitable antibodies are described in Ou et al. (Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV, Nature Communications (2020) 11:1620;
https://doi.org/10.1038/s41467-020-15562-9). In embodiments of the present invention, a skilled person can detect preservation of a native surface conformation of SARS-CoV-2 (or e.g. the S or N
protein thereof) via cross-reaction of such antibodies with the inactivated particles. In other words, the inactivated particles bind specifically to one or more anti-SARS-CoV-2 antibodies directed against
13 surface epitopes, preferably anti-S-protein antibodies, e.g. to antibodies generated against neutralizing epitopes in native SARS-CoV-2 virions.
The SARS-CoV-2 particles in the vaccine composition may be derived from any known strain of SARS-CoV-2, or variants thereof. For instance, the virus may be a strain as defined in Figure 2, or may comprise a nucleotide or amino acid sequence as defined therein, or a variant sequence having at least e.g. 95% sequence identity thereto. For instance, in one embodiment the SARS-CoV-2 particle comprises an RNA sequence corresponding to a DNA sequence (i) as defined in SEQ ID NO: 1 (which is also defined in NCBI Reference Sequence NC_045512.2). By "corresponding to", it will be understood that the defined DNA sequence is an equivalent of the viral RNA
sequence, i.e. is a DNA
or cDNA sequence that encodes the viral RNA or a sequence complementary to the viral RNA. As described herein, the inactivation process may result in modification (e.g.
alkylation or acylation) and/or fragmentation of viral RNA, and thus it will be understood that the inactivated viral particles may not comprise an intact RNA sequence as defined herein, but rather are derived from native viral particles which do comprise such a sequence.
The SARS-CoV-2 particles may also comprise variants of the known SARS-CoV-2 Wuhan-Hu-1 lineage or also referred to as the reference lineage, e.g. sequences having at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID NO: 1 and/or NCBI
Reference Sequence NC_045512.2. Preferably, the variant sequence encodes an infectious SARS-CoV-2 particle, e.g. a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence that is able to pack a virulent SARS-CoV-2 virus.
Further known SARS-CoV-2 particles may also comprise variants of the known SARS-CoV-2 South African lineage B.1.351, e.g. sequences having at least 85%, at least 90%, at least 95% or at least 99%
sequence identity to SEQ ID NO: 18 and/or NCBI Reference Sequence 1V1W598408.
Preferably, the variant sequence encodes an infectious SARS-CoV-2 particle, e.g. a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence that is able to pack a virulent SARS-CoV-2 virus. Further examples of variants of the known SARS-CoV-2 South African lineage B.1.351 are given in Figure 2.
Further known SARS-CoV-2 particles may also comprise variants of the known SARS-CoV-2 Brazilian lineage P.1, e.g. sequences having at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID NO: 20 and/or NCBI Reference Sequence MW520923. Preferably, the variant sequence encodes an infectious SARS-CoV-2 particle, e.g. a native (non-inactivated) SARS-CoV-2
14 particle comprising the RNA sequence that is able to pack a virulent SARS-CoV-2 virus. Further examples of variants of the known SARS-CoV-2 Brazilian lineage P.1 are given in Figure 2.
Further known SARS-CoV-2 particles may also comprise variants of the known SARS-CoV-2 UK
lineage B.1.1.7, e.g. sequences having at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID NO: 22 and/or NCBI Reference Sequence MW422256. Preferably, the variant sequence encodes an infectious SARS-CoV-2 particle, e.g. a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence that is able to pack a virulent SARS-CoV-2 virus. Further examples of variants of the known SARS-CoV-2 UK lineage B.1.1.7 are given in Figure 2.
Further known SARS-CoV-2 particles may also comprise variants of the known SARS-CoV-2 Californian lineages B.1.427 and B.1.429, e.g. sequences having at least 85%, at least 90%, at least 95%
or at least 99% sequence identity to SEQ ID NO: 24 and/or SEQ ID NO: 26.
Preferably, the variant sequence encodes an infectious SARS-CoV-2 particle, e.g. a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence that is able to pack a virulent SARS-CoV-2 virus. Further examples of variants of the known SARS-CoV-2 Californian lineages can be found in GenBank.
Similarly, in preferred embodiments the SARS-CoV-2 particle comprises an S
protein of the Wuhan lineage comprising or consisting of (i) an amino acid sequence as defined in SEQ ID NO: 3, or (ii) an amino acid sequence having at least 95%, at least 97% or at least 99% identity to SEQ ID NO: 3.
In further preferred embodiments the SARS-CoV-2 particle comprises an S
protein of the South African B1.351 lineage comprising or consisting of (i) an amino acid sequence as defined in SEQ ID NO: 19, or (ii) an amino acid sequence having at least 95%, at least 97% or at least 99% identity to SEQ ID NO:
19.
In further preferred embodiments the SARS-CoV-2 particle comprises an S
protein of the Brazilian P.1 lineage comprising or consisting of (i) an amino acid sequence as defined in SEQ ID NO: 21, or (ii) an amino acid sequence having at least 95%, at least 97% or at least 99% identity to SEQ ID NO: 21.
In further preferred embodiments the SARS-CoV-2 particle comprises an S
protein of the UK B.1.1.7 lineage comprising or consisting of (i) an amino acid sequence as defined in SEQ ID NO: 23, or (ii) an amino acid sequence having at least 95%, at least 97% or at least 99% identity to SEQ ID NO: 23.
In further preferred embodiments the SARS-CoV-2 particle comprises an S
protein of the Californian B.1.427 lineage comprising or consisting of (i) an amino acid sequence as defined in SEQ ID NO: 25, or (ii) an amino acid sequence having at least 95%, at least 97% or at least 99% identity to SEQ ID NO:
25.
In further preferred embodiments the SARS-CoV-2 particle comprises an S
protein of the Californian B.1.429 lineage comprising or consisting of (i) an amino acid sequence as defined in SEQ ID NO: 27, or (ii) an amino acid sequence having at least 95%, at least 97% or at least 99% identity to SEQ ID NO:
27.
In some embodiments, the inactivated SARS-CoV-2 particles are combined with other inactivated SARS-CoV-2 particles in the vaccine (other = other sequence).
In some embodiments, a combination of SARS-CoV-2 particles in the vaccine comprises or consists of at least two SARS-CoV-2 particles selected from the group consisting of i) the reference Wuhan_l lineage such as e.g. SEQ ID Nos: 1, 9, 12, 15; ii) the South African B.1.531 lineage such as e.g. SEQ
ID NO: 18; the Brazilian P.1 lineage such as e.g. SEQ ID NO: 20; the UK
B.1.1.7 lineage such as e.g.
SEQ ID NO: 22 and the Californian B.1.427 lineage such as e.g. SEQ ID NO: 24 or B.1.429 lineages such as e.g. SEQ ID NO: 26. A preferred embodiment is a combination comprising i) a Wuhan_l lineage such as e.g. SEQ ID NO: 9; and ii) a South African B.1.531 lineage such as e.g. SEQ ID NO: 18.
In a further embodiment, a combination of SARS-CoV-2 particles in the vaccine comprises or consists of at least three, e.g. three SARS-CoV-2 particles selected from the group consisting of i) the reference Wuhan_l lineage such as e.g. SEQ ID NOs 1, 9, 12, 15; ii) the South African B.1.531 lineage such as e.g. SEQ ID NO: 18; the Brazilian P.1 lineage such as e.g. SEQ ID NO: 20; the UK B.1.1.7 lineage such as e.g. SEQ ID NO: 22 and the Californian B.1.427 such as e.g. SEQ ID NO:
24 or B.1.429 lineages such as e.g. SEQ ID NO: 26. A preferred embodiment of such a trivalent vaccine is a combination comprising i) a Wuhan_l lineage such as e.g. SEQ ID NO: 9; and ii) a South African B.1.531 lineage such as e.g. SEQ ID NO: 18; and iii) an UK B.1.1.7 lineage such as e.g. SEQ ID
NO: 22. Another preferred embodiment of such a trivalent vaccine is a combination comprising i) a Wuhan_l lineage such as e.g. SEQ ID NO: 9; and ii) a South African B.1.531 lineage such as e.g. SEQ ID NO: 18; and iii) a Brazilian P.1 lineage such as e.g. SEQ ID NO: 20.
The similarity between amino acid sequences and/or nucleic acid sequences is expressed in terms of the similarity between the sequences, otherwise referred to as sequence identity.
Sequence identity is frequently measured in terms of percentage identity: the higher the percentage, the more similar the two sequences are. Homologs, orthologs, or variants of a polynucleotide or polypeptide will possess a relatively high degree of sequence identity when aligned using standard methods.
Methods of alignment of sequences for comparison are well known in the art.
Various programs and alignment algorithms are described in: Smith & Waterman, Adv. Appl. Math.
2:482, 1981; Needleman & Wunsch, Mol. Biol. 48:443, 1970; Pearson & Lipman, Proc. Natl. Acad. Sci.
USA 85:2444, 1988;
Higgins & Sharp, Gene, 73:237-44, 1988; Higgins & Sharp, CABIOS 5: 151-3, 1989; Corpet et al., Nuc. Acids Res. 16: 10881-90, 1988; Huang et al. Computer Appls. in the Biosciences 8, 155-65, 1992;
and Pearson et al., Meth. Mol. Bio. 24:307-31, 1994. Altschul et al, J. Mol.
Biol. 215:403-10, 1990, presents a detailed consideration of sequence alignment methods and homology calculations.
Once aligned, the number of matches is determined by counting the number of positions where an identical nucleotide or amino acid residue is present in both sequences. The percent sequence identity is determined by dividing the number of matches either by the length of the sequence set forth in the identified sequence, or by an articulated length (such as 100 consecutive nucleotides or amino acid residues from a sequence set forth in an identified sequence), followed by multiplying the resulting value by 100. Preferably, the percentage sequence identity is determined over the full length of the sequence. For example, a peptide sequence that has 1166 matches when aligned with a test sequence having 1554 amino acids is 75.0 percent identical to the test sequence (1l661554* 100=75.0). The percent sequence identity value is rounded to the nearest tenth. For example, 75.11, 75.12, 75.13, and 75.14 are rounded down to 75.1, while 75.15, 75.16, 75.17, 75.18, and 75.19 are rounded up to 75.2.
The length value will always be an integer.
The NCBI Basic Local Alignment Search Tool (BLAST) (Altschul et al., Mol.
Biol. 215:403, 1990) is available from several sources, including the National Center for Biotechnology Information (NCBI, Bethesda, MD) and on the internet, for use in connection with the sequence analysis programs BLASTP, BLASTN, BLASTX, TBLASTN and TBLASTX. A description of how to determine sequence identity using this program is available on the NCBI website on the internet. The BLAST
and the BLAST 2.0 algorithms are also described in Altschul et al., Nucleic Acids Res. 25:3389-3402, 1977. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information (ncbi.nlm.nih.gov). The BLASTN program (for nucleotide sequences) uses as defaults a word length (W) of 11, alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands. The BLASTP program (for amino acid sequences) uses as defaults a word length (W) of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff &
Henikoff, Proc. Natl.
Acad. Sci. USA 89: 10915, 1989).

Homologs and variants of a polynucleotide or polypeptide are typically characterized by possession of at least about 75%, for example at least about 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% sequence identity counted over at least 50, 100, 150, 250, 500, 1000, 2000, 5000 or 10,000 nucleotide or amino acid residues of the reference sequence, over the full length of the reference sequence or over the full length alignment with the reference amino acid sequence of interest.
Polynucleotides or proteins with even greater similarity to the reference sequences will show increasing percentage identities when assessed by this method, such as at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity. For sequence comparison of amino acid or nucleic acid sequences, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters arc designated. Default program parameters arc used.
One example of a useful algorithm is PILEUP. PILEUP uses a simplification of the progressive alignment method of Feng & Doolittle, Mol. Evol. 35:351-360, 1987. The method used is similar to the method described by Higgins & Sharp, CABIOS 5:151-153, 1989. Using PILEUP, a reference sequence is compared to other test sequences to determine the percent sequence identity relationship using the following parameters: default gap weight (3.00), default gap length weight (0.10), and weighted end gaps. PILEUP can be obtained from the GCG sequence analysis software package, e.g., version 7.0 (Devereaux et al., Nuc. Acids Res. 12:387-395, 1984).
As used herein, reference to "at least 80% identity" refers to at least 80%, at least 85%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or even 100% identity to a specified reference sequence, e.g. to at least 50, 100, 150, 250, 500, 1000, 5000 or 10,000 nucleotide or amino acid residues of the reference sequence or to the frill length of the sequence. As used herein, reference to "at least 90%
identity" refers to "at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99%, or even 100% identity" to a specified reference sequence, e.g. to at least 50, 100, 150, 250, 500, 1000, 5000 or 10,000 nucleotide or amino acid residues of the reference sequence or to the full length of the sequence.
In some embodiments, the inactivated SARS-CoV-2 particles are combined with an adjuvant in the vaccine. In some embodiments, the adjuvant is a Thl response-directing adjuvant. By this it is meant that when the vaccine is administered to a subject, the adjuvant promotes the induction of a predominantly T helper type 1 (i.e. Th 1) immune response in the subject (rather than a Th2 type response). The Thl- or Th2-directing properties of commonly used vaccines are known in the art. It has surprisingly been found that using an adjuvant that promotes a predominantly Thl response can improve immunogenicity of the vaccine and thus antiviral responses, as well as reducing a risk of disadvantageous effects such as immunopathology (which may result from a predominantly Th2 type response possibly due to hypersensitivity against viral components).
In some embodiments, the adjuvant comprises 3-0-desacy1-4'-monophosphoryl lipid A (MPL), saponin QS-21, a CpG-containing oligodeoxynucleotide (CpG ODN), squalene, DL-a-tocopherol, a cationic peptide, a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN) and/or imiquimod. For instance, examples of suitable adjuvants may comprise:
Adjuvant System 01 (AS01), which is a liposomal preparation comprising 3-0-desacy1-4'-monophosphoryl lipid A (MPL) and saponin QS-21; CpG 1018, a CpG ODN comprising the sequence 5' TGACTGTGAACGTTCGAGATGA (SEQ ID NO: 4); Adjuvant System 03 (AS03), comprising squalene, DL-a-tocopherol and polysorbate 80; IC31, comprising a peptide comprising the sequence KLKL5KLK (SEQ ID NO: 5) and an I-ODN comprising oligo-d(IC)13 (SEQ ID NO: 6);
or MF59, an oil-in-water emulsion comprising squalene, Tween 80 and Span 85.
In another embodiment, the vaccine or adjuvant does not comprise a CpG-containing oligodeoxynucleotide (CpG ODN). In another embodiment, the vaccine or adjuvant does not comprise CpG 1018, i .e . the vaccine or adjuvant does not comprise the sequence 5 TGACTGTGAACGTTCGAGATGA 3' (SEQ ID NO: 4).
In some embodiments, the dosage of a Thl promoting adjuvant, such as especially AS01, AS03, MF59, imiquimod or CpG, will be arrived at empirically. In some embodiments, the dosage of the Thl promoting adjuvant will be determined from previous studies.
In alternative embodiments, the adjuvant may comprise an aluminium salt, e.g.
aluminium oxide, aluminium hydroxide or aluminium phosphate. A preferred aluminium salt is the aluminium hydroxide with reduced Cu content, e.g. lower than 1.25 ppb based on the weight of the vaccine composition, an adjuvant described in detail in W02013/083726 or Schlegl et al.. Vaccine 33 (2015) 5989-5996. In some embodiments, an alum adjuvant is the only adjuvant in the vaccine composition. As referred to herein, the weight of the alum component refers to the weight of the Al' in the solution, regardless of what type of aluminium salt is used. For example, 0.5 mg of m- corresponds to 1.5 mg alum. In one embodiment, the amount alum (Al") present in the SARS-CoV-2 vaccine composition is between about 0.1 and 2 mg/mL, between about 0.2 and 1.5 mg/mL, between about 0.5 and 1.3 mg/mL, especially between about 0.8 to 1.2 mg/mL, most preferably about 1 mg/mL, i.e., 0.5 mg/dose. However the use of aluminium adjuvants alone is generally less preferred in the present invention, as they tend to direct a predominantly Th2 type immune response. Therefore in embodiments where the vaccine comprises an aluminium salt, it is particularly preferred that the vaccine further comprises a Thl-directing adjuvant, e.g. as described above.
Thus in one embodiment, the adjuvant may comprise an aluminium salt and a CpG
ODN, e.g. CpG
1018 (SEQ ID NO: 4). CpG 1018 can be adsorbed onto alum and, when used as a combinatorial adjuvant, has been shown to induce both Thl and Th2 responses (Tian. et al.
2017 Oncotarget 8(28)45951-45964); i.e. a more "balanced" immune response. Particularly, when administered in combination with alum, CpG has been shown to increase the overall magnitude of the immune response and to reduce the Th2 bias that is induced by conventional adjuvants such as alum (X P. Ioannou et al.
CpG-containing oligodeoxynucleotides, in combination with conventional adjuvants, enhance the magnitude and change the bias of the immune responses to a herpesvinis glycoprotein. 2002 Vaccine 21:127-137). The dose range for CpG in combination with alum may be anywhere between 10 ng and 3 mg.
Typically, the adjuvant is combined with the inactivated SARS-CoV-2 particles during manufacture of the vaccine product, i.e. the manufactured vaccine product comprises the adjuvant and is sold/distributed in this form. In alternative embodiments the adjuvant may be combined with the inactivated SARS-CoV-2 particles at the point of use, e.g. immediately before clinical administration of the vaccine (sometimes referred to as "bedside mixing" of the components of the vaccine). Thus the present invention comprises both vaccine products comprising inactivated SARS-CoV-2 particles and an adjuvant as described herein, as well as kits comprising the individual components thereof (e.g.
suitable for bedside mixing), and the combined use of the individual components of the vaccine in preventing or treating SARS-CoV-2 infection.
The SARS-CoV-2 vaccine may be produced by methods involving a step of inactivation of native SARS-CoV-2 particles, as described above. Generally, the native SARS-CoV-2 particles may be obtained by standard culture methods, e.g. by in vitro production in mammalian cells, preferably using Vero cells. For instance, the native SARS-CoV-2 particles may be produced using methods analogous to those described in e.g. WO 2017/109225 and/or WO 2019/057793, the contents of which are incorporated herein in their entirety, which describe methods for the production of Zika and Chikungunya viruses in Vero cells. The steps such as passaging, harvesting, precipitation, dialysis, filtering and purification described in those documents are equally applicable to the present process for producing SARS-CoV-2 particles.
For instance, in some embodiments, the method may comprise purifying the inactivated SARS-CoV-2 particles by one or more size exclusion methods such as (i) a sucrose density gradient centrifugation, (ii) a solid-phase matrix packed in a column comprising a ligand-activated core and an inactive shell comprising pores, wherein the molecular weight cut-off of the pores excludes the virus particles from entering the ligand-activated core, and wherein a molecule smaller than the molecular weight cut-off of the pores can enter the ligand-activated core and collecting the virus particles, and/or (iii) batch or size exclusion chromatography; to obtain purified inactivated SARS-CoV-2 particles.
Preferably, in the resulting purified preparation of viral particles, (i) the concentration of residual host cell DNA is less than 100 ng/mL; (ii) the concentration of residual host cell protein is less than 1 ng/mL; and (iii) the concentration of residual aggregates of infectious virus particles is less than 1 vtg/mL.
In some embodiments, the method may comprise a step of precipitating a harvested culture medium comprising SARS-CoV-2 particles, thereby producing native SARS-CoV-2 particles in a supernatant.
The precipitating step may comprise contacting the culture medium with protamine sulfate or benzonase. By using such a step, both contaminating DNA derived from host cells as well as immature and otherwise non-infectious virus particles can be separated from the preparation.
Moreover, protamine sulfate can be very efficiently separated from the virus fraction, e.g. using sucrose density centrifugation or a solid-phase matrix packed in a column comprising a ligand-activated core and an inactive shell comprising pores, wherein the pores comprise a molecular weight cut-off that excludes the virus particles from entering the ligand-activated core, and wherein a molecule smaller than the molecular weight cut-off of the pores (e.g. the protamine sulfate) can enter the ligand-activated coreรต allowing for a safer vaccine produced at high yields.
Thus the residual host cell DNA of the obtained virus preparation or vaccine may be less than 1 ng/mL, especially less than 900, 800, 700, 600, 500, 400, 300 or 200 ng/mL, preferably less than 150 or 100 ng/mL. In a preferred embodiment, the residual host cell DNA of the virus preparation or vaccine is less than 40 pg/mL. In some embodiments, the residual host cell protein of the virus preparation or vaccine is less than 10 ng/mL, especially less than 9, 8, 7, 6, 5, 4, 3 or 2 mg/mL, preferably less than 1 ng/mL. In a preferred embodiment, the residual host cell protein of the virus preparation or vaccine is less than 150 ng/mL. In some embodiments, the residual non-infectious virus particles of the virus preparation or vaccine is less than 10 pg/mL, especially less than 9, 8, 7, 6, 5, 4, 3 or 2 iag/mL, preferably less than 1 g/mL. In a preferred embodiment, the content of residual non-infectious virus particles of the virus preparation or vaccine is less than 100 ng/mL.
In some embodiments, the vaccine and/or SARS-CoV-2 particles may comprise residual protamine (e.g.
protamine sulfate), typically in trace amounts. In some embodiments, residual protamine (e.g.
protamine sulfate) in the virus preparation or vaccine is less than 2 ps/mL or 1 ug/mL, especially less than 900, 800, 700, 600, 500, 400, 300 or 200 ng/mL, preferably less than 100 ng/mL, more preferably is below the detection limit of HPLC, in particular below the detection limit in the final drug substance.
In some embodiments, the PS content is tested by HPLC or size exclusion chromatography (SEC). For example, HPLC is validated for PS determination in JEV sucrose gradient pool samples as a routine release assay and is very sensitive (i.e., limit of quantification (LOQ) 3 ug/mL; limit of detection (LOD) 1 ug/mL). In the current invention, PS content in SARS-CoV-2 drug substance was <LOD. In one embodiment, the HPLC assessment of PS contcnt can be performed on a Superdcx Peptide 10/300GL
column (GE: 17-5176-01) using 30% Acetonitrile, 0,1% Trifluoroacetic acid as solvent with a flow rate of 0.6 ml/min at 25 C and detection at 214 nm. A more sensitive method of measurement for residual protamine in a purified virus preparation is mass spectrometry (MS). In some embodiments, the residual PS levels in a Zika virus preparation are tested by MS or other such highly sensitive method, e.g. nuclear magnetic resonance (NMR). With this method, residual PS, as well as fragments and/or break-down products of PS, can be detected at trace amounts, such as levels as low as, for example, 106, 107 or 108 molecules per typical sample load. In some embodiments, the PS levels are tested in the drug product.
In some embodiments, the PS levels are tested in the drug substance.
Preferably an amount of the inactivating agent (e.g. beta-propiolactone) in the drug product or drug substance (e.g. vaccine composition) is very low, e.g. less than 100 ppm, less than 10 ppm, or less than 1 ppm (by weight).
The SARS-CoV-2 vaccine may be administered to a subject, preferably a mammalian subject, more preferably a human subject. Typically the SARS-CoV-2 vaccine is administered to a subject at risk of SARS-CoV-2 infection, e.g. in order to prevent SARS-CoV-2 infection and/or to prevent SARS-CoV-2 associated disease (COVID-19). The subject is preferably (i) an elderly subject (e.g. older than 65 years, 70 years or 80 years) (ii) a pregnant subject (iii) an immunocompromised subject or (iv) a child (e.g. a person younger than 18 years, 16 years, 14 years, 12 years, 10 years, 8 years, 6 years, 4 years, 2 years or younger). The SARS-CoV-2 vaccine described herein is advantageously capable of generating robust immune responses in subjects particularly susceptible or vulnerable to SARS-CoV-2-mobidity or mortality, i.e. immunocompromised, pregnant or elderly subjects. The SARS-CoV-2 vaccine may be administered to the subject in a single dose or two or more doses, e.g.
separated by intervals of about 7, 14,21 or 28 days.
In a preferred embodiment, on administration to a human subject the vaccine does not induce antibody-dependent enhancement (ADE) of SARS-CoV-2-associated disease (COVID-19). ADE
is a phenomenon by which virus-specific antibodies (e.g. as generated by vaccination) can enhance viral entry into host cells and/or viral replication. It is an advantage of the present invention that the inactivated SARS-CoV-2 vaccine described herein shows low or no ADE in human subjects, and can therefore be safely used for mass vaccination purposes. In particular, the vaccine described herein retains high quality immunogenic epitopes, which therefore results in high neutralizing antibody titers and diminishes the risk of ADE on administration to subjects. The risk of ADE
development may be assessed in non-human primates, as described in the Examples (see also Luo F.
et al. (2018), Virologicci Sin/ca 33:201-204).
In another preferred embodiment, on administration to a human subject the vaccine does not result in immunopathology. It is known that under some circumstances, a vaccine (e.g. a SARS-CoV vaccine) can result in e.g. a Th2-type immunopathology, e.g. a hypersensitivity response to SARS-CoV
components in animals. In embodiments of the present invention, a Thl type response is favored, e.g.
by use of a Thl-directing adjuvant (e.g. AS01 or another adjuvant as described herein). Especially, a balanced Th2/Th1-type immune response is preferred, such as that induced by use of a Th2-stimulating adjuvant, e.g., alum, combined with a Thl-stimulating adjuvant. The risk of immunopathology developing may be assessed in animal models, e.g. as described in Tseng C.T.
et al. (2012) PLoS ONE
7(4):e35421. In a preferred embodiment of the current invention, the vaccines of the invention show a shift in the Th2/Th1-type immune response to a Thl -type immune response compared to a vaccine adjuvanted with alum.
Any of the SARS-CoV-2 vaccines or compositions described herein may be administered to a subject in a therapeutically effective amount or a dose of a therapeutically effective amount. As used herein, a -therapeutically effective amount" of vaccine is any amount that results in a desired response or outcome in a subject, such as those described herein, including but not limited to prevention of infection, an immune response or an enhanced immune response to SARS-CoV-2, or prevention or reduction of symptoms associated with SARS-CoV-2 disease. More specifically, a therapeutic amount of the SARS-CoV-2 vaccine of the invention may be a total viral protein mass of between about 0.05 and 50 pg, more preferably between about 0.5 to 10 jig.

In some embodiments, the therapeutically effective amount of a SARS-CoV-2 vaccine or composition described herein is an amount sufficient to generate antigen-specific antibodies (e.g., anti-SARS-CoV-2 antibodies). In some embodiments, the therapeutically effective amount is sufficient to seroconvert a subject with at least 70% probability. In some embodiments, the therapeutically effective amount is sufficient to seroconvert a subject with at least 75%, 80%, 85% 90%, 95%, 96%, 97%, 98%, or at least 99% probability. Whether a subject has seroconverted can be assessed by any method known in the art, such as obtaining a serum sample from the subject and performing an assay to detect anti-SARS-CoV-2 antibodies. In some embodiments, a subject is seroconverted if a serum sample from the subject contains an amount of anti-SARS-CoV-2 antibodies that surpasses a threshold or predetermined baseline. A subject is generally considered seroconverted if there is at least a 4-fold increase in anti-SARS-CoV-2 antibodies (i.e., anti-SARS-CoV-2 S protein IgG antibodies) present in a serum sample from the subject as compared to a serum sample previously taken from the same subject.
In one embodiment, the dose of the inactivated SARS-CoV-2 virus in the vaccine composition of the current invention is between about 0.01 and 25 mAU (milli-absorption units x minutes as assessed by SEC-HPLC), preferably between about 0.05 and 10 mAU, more preferably between about 0.1 and 5 mAU, most preferably between about 0.25 and 2.5 mAU. In one embodiment, the dose is between about 0.05 and 50 lag total protein as measured by (jt)BCA assay, between about 0.1 and 25 jug, between about 0.25 and 12.5 jig, preferably between about 0.5 and 5 jAg total protein. More preferably the dose of the inactivated SARS-CoV-2 virus in the vaccine composition is at least 2.5 jig total protein, at least 3.5 pg total protein or at least 2.5 jig total protein, e.g. the vaccine composition comprises 2.5 jig to 25 jig, 3.5 jig to 10 jig or 4 jig to 6 jig total protein/dose, preferably about 5 jig total protein/dose. In some embodiments, the dosage is determined by the total amount of S protein in the inactivated SARS-CoV-2 formulation, as assessed by e.g. ELISA. The mass of antigen may also be estimated by assessing the SE-HPLC peak area per dose equivalent (recorded as milli-absorption units x minutes; mAU), which is estimated to be approximately 2 pg/m1 total surface protein and approximately 1 jig/mL S-protein. In one embodiment, the dose is between about 0.025 and 25 jig S-protein as measured by ELISA, between about 0.05 and 12.5 vg, between about 0.125 and 6.25 jig, preferably between about 0.25 and 2.5 jig S-protein.
In a preferred embodiment, the amount of antigen in the SARS-CoV-2 vaccine is determined by ELISA.
In one embodiment, the ELISA measures a SARS-CoV-2 protein or portion of a protein, e.g., nucleocapsid (N), membrane (M) or spike (S) protein; i.e., the ELISA utilizes a coating antibody specific to a SARS-CoV-2 protein or portion of a protein. In a preferred embodiment, the coating antibody is specific to the SARS-CoV-2 Spike protein S1 subunit, e.g. residues 14-685 (or 14-683) of the S-protein sequence of SEQ ID NO:3, 19, 21, 23, 25 or 27, or to the Receptor Binding Domain (RBD), e.g. residues 331 to 528 (or 319 to 541) of the S-protein sequence of SEQ ID NO:3, 19, 21, 23, 25 or 27 (see Figure 9). In one embodiment, the ELISA readout is a mass per unit measure of the detected protein, e.g. iag/mL S-protein. In a preferred embodiment, the standard used is a spike protein trimer and the results of the SARS-CoV-2 ELISA are reported as "antigen units"
(AU), corresponding to the ACE-2 binding ability of the standard protein (determined by the manufacturer).
In one embodiment, the amount of SARS-CoV-2 antigen administered to a subject is between about 1 to 100 AU/dose, preferably between about 2 to 75 AU/dose, preferably between about 3 and 60 AU/dose, more preferably between about 3 and 55 AU/dose, more preferably between about 3 and 53 AU/dose. In an even more preferred embodiment, the amount of SARS-CoV-2 antigen administered to a subject is 3 AU, 10 AU or 40 AU per dose, most preferred 40 AU per dose. In further preferred embodiments, the amount of SARS-CoV-2 antigen administered to a subject is at least 10 AU/dose, at least 20 AU/dose, at least 25 AU/dose or at least 30 AU/dose, e.g. about 10 to 60 AU/dose, 20 to 50 AU/dose, 25 to 45 AU/dose or 30 to 40 AU/dose, e.g. about 35 AU/dose. The amount of SARS-CoV-2 antigen (e.g. in AU/dose) may be assessed, for example, by a SARS-CoV-2 ELISA assay as described in Example 1. It is estimated that there are about 1 to 1.5 x 10 viral particles per AU, and the amounts of SARS-CoV-2 antigen described above may be construed accordingly. Thus in some embodiments, the amount of SARS-CoV-2 antigen administered to a subject is between about 1.5 x 107 to 1.5 x 109 viral particles/dose, or between about 4.5 x 107 to 9.0 x 108 viral particles/dose, e.g. at least 1.5 x 108 viral particles/dose or at least 3.0 x 108 viral particles/dose, about 1.5 x 108 to 7.5 x 108 viral particles/dose or about 4.5 x 108 to 6.0 x 108 viral particles/dose.
In some embodiments, seroconversion of a subject is assessed by performing a plaque reduction neutralization test (PRNT). Briefly, PRNT is used to determine the scrum titer required to reduce the number of SARS-CoV-2 plaques by 50% (PRNT50) as compared to a control serum/antibody. The PRNT50 may be carried out using monolayers of Vero cells or any other cell type/line that can be infected with SARS-CoV-2. Sera from subjects are diluted and incubated with live, non-inactivated SARS-CoV-2. The serum/virus mixture may be applied to Vero cells and incubated for a period of time.
Plaques formed on the Vero cell monolayers are counted and compared to the number of plaques formed by the SARS-CoV-2 in the absence of scrum or a control antibody. A threshold of neutralizing antibodies of 1:10 dilution of serum in a PRNT50 is generally accepted as evidence of protection in the case of JEV (Hombach et. al. Vaccine (2005) 23:5205-5211).
In some embodiments, the SARS-CoV-2 particles may be formulated for administration in a composition, such as a pharmaceutical composition. The term "pharmaceutical composition" as used herein means a product that results from the mixing or combining of at least one active ingredient, such as an inactivated SARS-CoV-2, and one or more inactive ingredients, which may include one or more pharmaceutically acceptable excipient. A preferred pharmaceutically acceptable excipient is human serum albumin (HSA), such as, especially recombinant HSA (rHSA). In one embodiment, the SARS-CoV-2 vaccine of the invention contains about 10 to 50 tg HSA/dose, preferably about 20 to 40 pig HSA/dose, more preferably about 25 to 35 pig HSA/dose.
Pharmaceutical compositions of the invention, including vaccines, can be prepared in accordance with methods well known and routinely practiced in the art (see e.g., Remington:
The Science and Practice of Pharmacy, Mack Publishing Co. 20th ed. 2000; and Ingredients of Vaccines ยจ
Fact Sheet from the Centers for Disease Control and Prevention, e.g., adjuvants and enhancers as described above to help the vaccine improve its work, preservatives and stabilizers to help the vaccine remain unchanged (e.g., albumin, such as human serum albumin (HSA) or recombinant HSA (rHSA), phenols, glycine)). As used herein, the term "vaccine" refers to an immunogenic composition, e.g. a composition capable of inducing an immune response in a (human) subject against an antigen (e.g.
against a SARS-CoV-2 antigen). For instance, the vaccine or composition may be capable of generating neutralizing antibodies against SARS-CoV-2. In some embodiments, the vaccine or composition is capable of generating antibodies (e.g. IgG) against SARS-CoV-2 S (spike) protein. In some embodiments, the vaccine or composition is capable of generating a T cell response against SARS-CoV-2 proteins or peptides, for instance a T cell response against a SARS-CoV-2 S-protein, membrane (M) protein and/or nucleocapsid (N) protein or peptides derived therefrom. Preferably the vaccine or immunogenic composition generates neutralizing antibodies and a T cell response against SARS-CoV-2.
Typically the vaccine or immunogenic composition is capable of inducing a protective effect against a disease caused by the antigen, e.g. a protective effect against SARS-CoV-2 infection (e.g.
symptomatic and/or asymptomatic infection) and/or COVID-19 disease).
Pharmaceutical compositions are preferably manufactured under GMP conditions.
Typically, a therapeutically effective dose of the inactivated SARS-CoV-2 vaccine preparation is employed in the pharmaceutical composition of the invention. The inactivated SARS-CoV-2 particles are formulated into pharmaceutically acceptable dosage forms by conventional methods known to those of skill in the art. Dosage regimens are adjusted to provide the optimum desired response (e.g., the prophylactic response).
Dosages of the active ingredients in the pharmaceutical compositions of the present invention can be varied so as to obtain an amount of the active ingredient which is effective to achieve the desired pharmaceutical response for a particular subject, composition, and mode of administration, without being toxic to the subject. The selected dosage level depends upon a variety of pharmacokinetic factors, including the activity of the particular compositions of the present invention employed, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the subject being treated, and like factors.
A physician, veterinarian or other trained practitioner, can start dosing of the inactivated SARS-CoV-2 vaccine employed in the pharmaceutical composition at levels lower than that required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect (e.g., production of anti-SARS-CoV-2 virus antibodies) is achieved. In general, effective doses of the compositions of the present invention, for the prophylactic treatment of groups of people as described herein vary depending upon many different factors, including means of administration, target site, physiological state of the patient, whether the patient is human or an animal, other medications administered, and the titer of anti-SARS-CoV-2 antibodies desired. Dosages need to be titrated to optimize safety and efficacy. In some embodiments, the dosing regimen entails subcutaneous or intramuscular administration of a dose of inactivated SARS-CoV-2 vaccine twice, once at day 0 and once at about day 7.
In some embodiments, the dosing regimen entails subcutaneous administration of a dose of inactivated SARS-CoV-2 vaccine twice, once at day 0 and once at about day 14. In some embodiments, the dosing regimen entails subcutaneous administration of a dose of inactivated SARS-CoV-2 vaccine twice, once at day 0 and once at about day 28. In some embodiments, the inactivated SARS-CoV-2 vaccine is administered to the subject once. In a preferred embodiment, the SARS-CoV-2 vaccine is administered to the subject more than once, preferably two times. In a preferred embodiment, the vaccine is administered on day 0 and day 21. In another preferred embodiment, the vaccine is administered on day 0 and day 28.
In further embodiments, a first (prime) dose of the inactivated SARS-CoV-2 vaccine is administered and a second (boost) dose of the inactivated SARS-CoV-2 vaccine is administered at least 28 days, at least 60 days, at least 70 days, at least 80 days or 90 days after the first dose. Thus in some embodiments, the second dose of the inactivated SARS-CoV-2 vaccine is administered 30 to 120 days or 1 to 4 months (preferably about 3 months) after the first dose.
In other embodiments, the inactivated SARS-CoV-2 vaccine is administered as a booster dose only, e.g.
a first (prime) dose of a (different) SARS-CoV-2 vaccine is administered and then a second (boost) dose of the inactivated SARS-CoV-2 vaccine is administered, e.g. at least 7, 14, 21, 28, 60 or 90 days after the first dose. The first (prime) dose of the SARS-CoV-2 vaccine may comprise any other vaccine or immunogenic composition that stimulates an immune response and/or a protective effect in subjects against SARS-CoV-2 virus. For example, the first dose of SARS-CoV-2 vaccine may comprise a recombinant viral vector or an mRNA sequence encoding one or more SARS-CoV-2 proteins and/or fragments thereof, e.g. a SARS-CoV-2 spike (S) protein. Alternatively the first dose of SARS-CoV-2 vaccine may comprise a subunit vaccine, e.g. comprising one or more SARS-CoV-2 proteins and/or fragments thereof, e.g. a SARS-CoV-2 spike (S) protein or fragment thereof.
Also within the scope of the present disclosure are kits for use in prophylactic administration to a subject, for example to prevent or reduce the severity of SARS-CoV-2 infection. Such kits can include one or more containers comprising a composition containing inactivated SARS-CoV-2, such as an inactivated SARS-CoV-2 vaccine. In some embodiments, the kit may further include one or more additional components comprising a second composition, such as a second vaccine, e.g. a second kind of SARS-CoV-2 vaccine that applies a different technology than in the first dose. In some embodiments, the second vaccine is a vaccine for an arbovirus. In some embodiments, the second vaccine is a Japanese encephalitis virus vaccine, a Zika virus vaccine, a Dengue virus vaccine and/or a Chikungunya virus vaccine.
In some embodiments, the kit can comprise instructions for use in accordance with any of the methods described herein. The included instructions can comprise a description of administration of the composition containing inactivated SARS-CoV-2 vaccine to prevent, delay the onset, or reduce the severity of SARS-CoV-2 infection. The kit may further comprise a description of selecting a subject suitable for administration based on identifying whether that subject is at risk for exposure to SARS-CoV-2 or contracting a SARS-CoV-2 infection. In still other embodiments, the instructions comprise a description of administering a composition containing inactivated SARS-CoV-2 vaccine to a subject at risk of exposure to SARS-CoV-2 or contracting SARS-CoV-2 infection.
The instructions relating to the use of the composition containing inactivated SARS-CoV-2 vaccine generally include information as to the dosage, dosing schedule, and route of administration for the intended treatment. The containers may be unit doses, bulk packages (e.g., multi-dose packages) or sub-unit doses. Instructions supplied in the kits of the invention are typically written instructions on a label or package insert (e.g., a paper sheet included in the kit), but machine-readable instructions are also acceptable.
The kits of the present disclosure are in suitable packaging. Suitable packaging includes, but is not limited to, vials, bottles, jars, flexible packaging, and the like. Also contemplated are packages for use in combination with a specific device, such as a syringe or an infusion device. The container may have a sterile access port, for example the container may be a vial having a stopper pierceable by a hypodermic injection needle. At least one active agent in the composition is an inactivated SARS-CoV-2, as described herein.
This invention is not limited in its application to the details of construction and the arrangement of components set forth in the following description or illustrated in the drawings. The invention is capable of other embodiments and of being practiced or of being carried out in various ways. Also, the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including", "comprising", or "having", "containing", "involving", and variations thereof herein, is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
Unless otherwise defined herein, scientific and technical terms used in connection with the present disclosure shall have the meanings that arc commonly understood by those of ordinary skill in the art.
Further, unless otherwise required by context, singular terms shall include pluralities and plural terms shall include the singular. The methods and techniques of the present disclosure are generally performed according to conventional methods well-known in the art. Generally, nomenclatures used in connection with, and techniques of biochemistry, enzymology. molecular and cellular biology, microbiology, virology, cell or tissue culture, genetics and protein and nucleic chemistry described herein are those well-known and commonly used in the art. The methods and techniques of the present disclosure are generally performed according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout the present specification unless otherwise indicated.
The present invention is further illustrated by the following examples, which in no way should be construed as further limiting. The entire contents of all of the references (including literature references, issued patents, published patent applications, and co-pending patent applications) cited throughout this application are hereby expressly incorporated by reference, in particular for the teaching that is referenced hereinabove. However, the citation of any reference is not intended to be an admission that the reference is prior art.

EXAMPLES
Example 1. Drug substance production For the production of SARS-CoV-2, the JEV process platform (Srivastava et al., Vaccine 19 (2001) 4557-4565; US 6,309,650B1) was used as a basis, also taking into account improvements in the process as adapted to Zika virus purification as disclosed in W02017/109223A1 (which is incorporated herein in its entirety). Briefly, non-infectious SARS-CoV-2 particle aggregates, host cell proteins and other low molecular weight impurities are removed by protamine sulfate precipitation or benzonase treatment and the resulting preparation is optionally further purified by sucrose gradient centrifugation. See Fig.
1 for an outline of the production process.
The first SARS-CoV-2 isolate from Italy, identified and characterized at the National Institute for Infectious Diseases "Lazzaro Spallanzani" IRCCS, Rome, Italy (Accession No:
MT066156), the RNA
sequence thereof corresponding to the DNA sequence provided by SEQ ID NO: 9, was used in all Examples disclosed herein. Other novel coronavirus SARS-CoV-2 isolates may also be obtained from the following sources:
1. -EVAg (European Virus Archive), e.g. one of the following strains:
B etaCoV/France/ID F0372/2020 (Ref-S KU: 014V-03890, https://www.european-virus-archive.com/virus/human-2019-ncov-0); 2019-nCoV/Italy-1NMI1, (Ref-S KU: 008V-03893, SEQ ID
NO: 9; httos ://www .curoncan-virus-archivc .com/virus/hurnan-2019-ncov-strain-2019-ncovitalv-inmil); BetaCoV/Netherlands/01, (Ref-S KU : 010V-03903, httos://www.eurovean-virus-archive.com/virus/sars-cov-2-strain-n12020) 2. -BEI Resources (Biodefense and Emerging Infections Research Resources):
e.g. Isolate USA-WA1/2020, NIAID, NIH: SARS-Related Coronavirus 2, NR-52281 (GenBank accession MN985325).
3. ยจPHE (Public Health England):
littps://www.gov.uk/govemment/collections/contacts-public-health-enaland-regions-local-centres-and-emergency: e.g. isolate of UK B.1.1.7 (UK_MIG457: EVAg Ref-SKU: 004V-04032; SEQ ID NO: 22) or South African B.1.531 (SA P2: EVAg Ref-SKU: 004V-04071; SEQ ID NO: 18) lineage Cell buildup and infection with SARS-CoV-2. The Vero cells used in the methods described herein were the VERO (WHO) cell line, obtained from the Health Protection Agency general cell collection under catalogue number 88020401, from which a master cell bank was generated.
A research master seed bank (rMSB) of SARS-CoV-2 (strain used 2019-nCoV/Italy-INMI1) was prepared on Vero cells and the genomic sequence was checked by sequencing. For production of SARS-CoV-2, Vero cells were grown in Eagle's minimal essential medium (EMEM) containing 10% fetal bovine serum (FBS) and monolayers were infected with SARS-CoV-2 at a multiplicity of infection (moi) of 0.001 to 1, preferably 0.01, plaque forming units (pfu) per cell. After allowing virus adsorption, the cultures were washed 2-4 times with PBS, fed with serum-free EMEM and incubated at 35 C with 5% CO2 until the virus titer reaches a desired level.
SARS-CoV-2 harvest. The culture medium was harvested at days 2, 3, 5 and 7 and harvests were pooled and centrifuged in a standard centrifuge. The resulting supernatant was filtered, followed by TFF
ultrafiltration to remove cell culture medium components and reduce batch volume. Host cell DNA and protein reduction as well as reduction of non-infectious virus aggregates in the concentrated material was achieved by precipitation with protamine sulfate. Protamine sulfate was added to the diafiltrated SARS-CoV-2 material to a final nominal concentration of ยจ2 mg/mL, while stirring, followed by incubation at 2-8 C for 30 minutes. Alternatively, the diafiltrated SARS-CoV-2 material was treated with benzonase.
Optional primary inactivation. The SARS-CoV-2 virus was inactivated by treatment with beta-propiolactone directly after removal of virus-containing cell culture medium from Vero cells, in order to render the virus safe to handle at BSL2. Inactivation is possible at any stage in the purification process, however, such as e.g., after centrifugation, before, during or after treatment with protamine sulfate or benzonase or before or after sucrose gradient centrifugation.
Inactivation is carried out by the use of a chemical inactivation agent such as formaldehyde (foririalin);
enzyme; beta-propiolactone;
ethanol; trifluroacetic acid: acetonitrile; bleach: urea; guanidine hydrochloride; tri-n-butyl phosphate:
ethylene-imine or a derivative thereof; an organic solvent, optionally Tween, Triton, sodium deoxycholate, or sulfobetaine; or a combination thereof. It is particularly preferred that inactivation is carried out using beta-propiolactone, which preferentially targets viral RNA
whilst relatively sparing viral surface proteins and their immunogenic epitopes. Inactivation may also be achieved by pH changes (very high or very low pH), by heat treatment or by irradiation such as gamma irradiation or UV
irradiation, particularly UV-C irradiation. The SARS-CoV-2 virus is optionally inactivated by two separate inactivation steps, such as, e.g. beta-propiolactone treatment and UV-C irradiation.
Evaluation of BPL starting concentration for inactivation of a highly resistant model virus (PPV). A
preliminary study for evaluation of PPV virus inactivation kinetics was conducted to initially support our proposed SARS-CoV-2 BPL inactivation procedure. Porcine Parvovirus (PPV) was selected as a model virus to evaluate the inactivation capability of BPL in aqueous solution because of its high resistance to physico-chemical inactivation. Three starting concentrations of BPL were evaluated: 300 ppm (1/3333), 500 ppm (1/2000) and 700 ppm (1/1429). Virus solution was spiked with BPL at these concentrations and incubated at 5+2 C for 24 hours. Kinetic samples were taken at 0.5, 2, 6, 24h and after the BPL hydrolyzation step and analysed for remaining infectivity. The results are shown in Table A.
Table A: Summary of virus titers and reduction factors for PPV
inactivation by BPL concentration [ppm]

titer w/o BPL 9.97 10.04 9.98 [TCID50/mL]
titer 6.66 4.98 4.1 24hincubation [TCID50/mL]
titer after 5.1 2.6** <LOD.*
hydrolysis [TCID50/mL]
reduction factor 4.84 0.39 7.43 0.92 >6.89 0.23 after hydrolysis *below limit of detection **Note limit of detection for 500ppm BPL is lower than for 700ppm BPL
A clear effect of initial BPL concentration on the inactivation effectivity was observed with a reduction between 3.3 and 5.9 log10 after 24h incubation at 5+2 C (before hydrolysis).
The following hydrolysis step further reduced the titers by on average addition 1.7 log10 while the hold control titers remained constant throughout the whole procedure. This indicated that for highly resistant virus contaminations the hydrolysis step might serve as an additional inactivation step. With overall reduction factors of 4.84 (300 ppm), 7.43 (500 ppm) and below the limit of detection (700 ppm) the applied BPL treatment was considered effective for the inactivation of Parvoviridac at concentrations >
300ppm. Therefore, we decided to select 500ppm for SARS-CoV-2 virus inactivation in all further studies.
SARS-CoV-2 virus inactivation by BPL
Based on existing data on the inactivation of model viruses by BPL (see section above on PPV
inactivation) a BPL concentration of 500 ppm (1/2000) was selected for the inactivation of SARS-CoV-2 virus harvest material. As the stability of BPL in solutions is highly temperature dependent an incubation temperature of 5+3 C and an incubation time of 24 hours were selected to ensure enough BPL present throughout the whole inactivation. After addition and mixing of BPL to the concentrated harvest, the inactivation solution is transferred to a fresh container where the inactivation takes place under controlled conditions. This transfer excludes the possibility of virus particles in potential dead-spots during initial mixing not being in contact with BPL.
To stabilize the pH of the inactivated viral solution during hydrolysis of the BPL, protamine sulfate (PS) treated concentrated harvest pre-cooled to 5 3 C is supplemented with 25 mM HEPES pH 7.4.
To reduce remaining BPL after the inactivation the solution is warmed to temperatures above 32 C for a total time of 2.5 hours + 0.5 hours in a temperature-controlled incubator set to 37+2 C. The total time of the hydrolyzation step for the current process volume of about 1L was between 5 hours 15 minutes and 6 hours 15 minutes including the warming to and the incubation above 32 C.
After completion of the hydrolysis, the inactivated viral solution (IVS) was immediately cooled down to 5+3 C in a temperature-controlled fridge and stored there until inactivation was confirmed by large volume plaque assay and serial passaging assay which currently requires 18 days in total. Recovery of virus particles throughout the inactivation process was monitored by size-exclusion chromatography.
Initial studies at lab-scale from 15 mL up to 1000mL indicated a very fast inactivation kinetic for SARS-CoV-2 where virus titers of up to 8 log10 pfu/mL were reduced below detectable levels within 2 hours after BPL addition. These results were confirmed for GMP production runs at a final inactivation volume of approximately 1L. Taken together with the inactivation data for model viruses the applied BPL treatment can be considered efficient and includes a significant safety margin for inactivation of SARS-CoV-2 concentrated harvest material.
In a further preferred embodiment, the inactivation step(s) are particularly gentle, in order to preserve surface antigen integrity, especially integrity of the S protein. In one embodiment, the gentle inactivation method comprises contacting a liquid composition comprising SARS-CoV-2 particles with a chemical viral inactivating agent (such as e.g. any of the chemical inactivation agents as listed above or a combination thereof, preferably beta-propiolactone) in a container, mixing the chemical viral inactivating agent and the liquid composition comprising SARS-CoV-2 particles under conditions of laminar flow but not turbulent flow, and incubating the chemical viral inactivating agent and the liquid composition comprising SARS-CoV-2 particles for a time sufficient to inactivate the viruses. The gentle inactivation step is optionally performed in a flexible bioreactor bag. The gentle inactivation step preferably comprises five or less container inversions during the period of inactivation. Preferably, the mixing of the chemical viral inactivating agent and the composition comprising SARS-CoV-2 particles comprises subjecting the container to rocking, rotation, orbital shaking, or oscillation for not more than minutes at not more than 10 rpm during the period of incubation.
Purification of SARS-CoV-2. Optionally, the material was immediately further processed by batch 5 adsorption (also known herein as batch chromatography) with CaptoTM Core 700 or CC400 chromatography media at a final concentration of ยจ1% CC700 or CC400. The material was incubated at 4 C for 15 minutes under constant agitation using a magnetic stirrer. After incubation, if used, the CC700 or CC400 solid matter was allowed to settle by gravity for 10 minutes and the SARS-CoV-2 material is removed from the top of the solution in order to avoid blockage of the filter by CaptoCore 10 particles. Any remaining CaptoCore particles and DNA precipitate were then removed from the solution by filtration using a 0.2 pm Mini Kleenpak EKV filter capsule (Pall). The pooled filtered harvest material was adjusted to a final concentration of 25 mM Tris pH 7.5 and 10%
sucrose (w/w) using stock solutions of both components. This allowed for freezing the concentrated harvest at <-65 C if required.
The resulting filtrate is further processed by sucrose density gradient centrifugation (also known herein as batch centrifugation) for final concentration and polishing of the SARS-CoV-2 material. The concentrated protamine sulfate (PS) or benzonase, preferred is PS, treated harvest was loaded on top of a solution consisting of three layers of sucrose with different densities. The volumes of individual layers for a centrifugation in 100 mL bottle scale are shown in Table la.
Table la: Volumes for sucrose density centrifugation.
Sucrose solution (w/w) Volume (mL) PS-treated SARS-CoV-2 harvest 40 (10% sucrose)
15% sucrose 15 35% sucrose 15 50% sucrose 20 Total volume 90 The sucrose gradient bottles were prepared by stratifying the individual sucrose layers by pumping the solutions into the bottom of the bottles, starting with the SARS-CoV-2 material with the lowest sucrose density (10% sucrose (w/w)), followed by the other sucrose solutions in ascending order. The described setup is shown in Figure 3. The prepared SG bottles were transferred into a rotor pre-cooled to 4 C and centrifuged at ยจ11,000 RCF max at 4 C for at least 20 hours, without brake/deceleration.

After centrifugation, harvest of serial 2 mL fractions of the sucrose gradient is performed from the bottom up with a peristaltic pump. The fractions were immediately tested by SDS-PAGE / silver staining to identify virus-containing fractions with sufficiently high purity.
Thus, identified fractions were pooled and further processed. The purified SARS-CoV-2 was stored at <-65 C or immediately formulated.
Formulation of SARS-CoV-2 with adjuvant. The SARS-CoV-2 particles were formulated with alum.
Optionally, a Thl adjuvant was also added to the formulation or provided as a separate composition for bedside mixing.
SARS-CoV-2 ELISA Assay. Inactivated SARS-CoV-2 antigen content (i.e. content of Si as the major antigenic protein) in preparations described herein was determined (quantified) by ELISA. The SARS-CoV-2 ELISA used herein is a four-layer immuno-cnzymatic assay with a SARS-CoV-2 spike antibody (AM001414; coating antibody) immobilized on a microtiter plate to which the SARS-CoV-2 sample is added. On binding of the antigen to the coating antibody, the plate was further treated with primary antibody (i.e. AbFlexlz)SARS-COV-2 spike antibody (rAb) (AM002414)). This was followed by addition of the secondary antibody, which is an enzyme linked conjugate antibody (i.e. Goat anti-Mouse IgG HRP Conjugate). The plates were washed between various steps using a mild detergent solution (PBS-T) to remove any unbound proteins or antibodies. The plate was developed by addition of a tetramethyl benzidine (TMB) substrate. The hydrolyzed TMB forms a stable colored conjugate that is directly proportional to the concentration of antigen content in the sample.
The antigen quantification was carried out by spectrophotometric detection at k450nm (2\,630nm reference) using the standard curve generated in an automated plate reader as a reference. Standards were prepared starting with a 20 antigen units (AU)/mL spike trimer working solution neat, which was further serially diluted 1:2 for the following standard concentrations: 20 AU/mL, 10 AU/mL, 5 AU/mL, 2.5 AU/mL, 1.25 AU/mL, 0.625 AU/mL, 0.3125 AU/mL and 0.1263 AU/mL. Each dilution was tested in duplicate per plate. An "antigen unit" of the spike trimer standard, according to the supplier (R&D
Systems), corresponds to its binding ability in a functional ELISA with Recombinant Human ACE-2 His-tag.
Reference Standards and Antibodies:
Coating Antibody: SARS-CoV-2 Spike Antibody (AM001414) Spike Trimcr (S 1+S2), His-tag (SARS-CoV-2) (e.g. BPS Lot# 200826; Cat#100728) SARS-CoV-2 QC (e.g. RSQC240920AGR) Primary Detection Antibody AbFlexl_t_, SARS-CoV-2 Spike Antibody (rAb) (AM002414) Secondary Detection Antibody Goat anti-Mouse 1gG HRP Conjugate Coating buffer: Carbonate buffer ELISA wash buffer: PBS + 0.05% Tween-20 (PBS-T).
Sample dilution buffer: PBS-T 1% BSA.
The production process delivered high density and intact spike proteins (see Figure 6). Estimated were about 1 to 1.5 x 107 viral particles per AU. Inactivation process by beta propiolactone provided for a fast inactivation kinetic and no detectable chemical modification of the S-protein. Key parameters and relevant process related impurities were similar to the commercial IXIAROCk production process (see Table lb). SARS-CoV-2 drug substance according to the invention was highly pure (>95%) according to SDS-PAGE (silver stain, reduced) and free from aggregates (monomer virus (>95%) according to SE-HPLC (see Figure 7).
Further confirmatory studies aimed at characterizing modifications of S-protein following beta-propiolactone-inactivated SARS-CoV-2 are carried out by mass spectrometric analysis oftryptic digests of the S-protein. The modification of amino acids in important epitopes is minimal. Initial alignment of receptor binding domains (RBD) within the S protein and hACE2 interfaces and epitopes of several known (cross)-neutralizing antibodies (SARS-CoV and SARS-CoV-2) have shown no amino acids within these epitopes with potential high conversion and only few with potential lower conversion rates.
Table lb. Comparison of key parameters and relevant process related impurities of the SARS-CoV-2 drug substance and IXIAROO drug substance.
SARS-CoV-2 IXIARO
Viral yield at harvest (login PFU/mL) > 7.8 > 7.3 Residual host cell protein (HCP) <150 <100 (ng/mL) =
Residual host cell DNA (hcDNA) (pg/mL) < LOQ <LOQ
(LOQ 40 pg/mL) Virus Monomer by SEC-MALLS (%) >95 >95 Residual Protamine sulfate* (itig/mL) < LOQ < LOQ
(LOQ 2 ug/mL) Endotoxins (EU/mL) <0.05 <0.05 < LOQ
< Residual Inactivation reagent LOQ (LOQ 50 ppm, (LOQ 1 ppm, 13-Propiolactonc) Formalin) Example 2. In vitro and in vivo assessment of immunogenicity and protective capacity of inactivated SARS-CoV-2 virus compositions Immunogenicity. Prior to immunization, experimental groups of 10 Balb/c mice were bled and pre-immune sera are prepared. The mice were administered a dose titration of inactivated SARS-CoV-2 formulated with alum subcutaneously (see Table 2). At two different intervals after immunization (see below), blood was collected and immune sera prepared, spleens were collected at the final bleed. All animal experiments were carried out in accordance with Austrian law (BGB1 Nr.
501/1989) and approved by -Magistratsabteilung 58". Sera were assessed for total IgG and subclasses (IgGI/IgG2a) by ELISA and neutralizing antibodies by PRNT. Th1/Th2 responses were further assessed by IFN-y ELISpot and intracellular cytokine staining (CD4+/CD8 ).
-Schedule 1: Immunizations Day 0/Day 7, interim bleed Day 14, final bleed and spleen harvest Day 28 -Schedule 2: Immunizations Day 0/Day 21, interim bleeds Day 14/Day 28, final bleed and spleen harvest Day 35 Table 2. Design of dosing experiments, 10 mice/group: 3 dosage groups: 0.2 - 2 lag total protein, number of experiments: 3. For experimentation purposes, the Thl adjuvant is added directly to the SARS-CoV-2/alum formulation before immunization of the mice.
Adjuvants (mice/group) Aluminium Inactivated Aluminium Thl hydroxide SARS-CoV- w/o hydroxide adjuvant (50jag)-ETh1 adjuvant 2 dosages (50 jag) (tbd) adjuvant (tbd) 2 ng 10 10 10 10 0.8 lag 10 10 10 10 0.2 ng 10 10 10 10 Placebo 10 10 10 10 Plaque reduction neutralization test (PRATT). Each well of a twelve-well tissue culture plate was seeded with Vero cells and incubated 35 C with 5% CO2 for three days. Serial dilutions from pools of heat-inactivated sera from each treatment group are tested. Each serum preparation was incubated with approximately 50-80 pfu of SARS-CoV-2 at 35 C with 5% CO2 for 1 hour. The cell culture medium was aspirated from the Vero cells and the SARS-CoV-2 /serum mixtures were added to each well. The plates are gently rocked and then incubated for 2 hours at 35 C with 5% CO2.
To each well, 1 mL of a 2% methylcellulose solution containing EMEM and nutrients are added, and the plates were further incubated for 4 days at 35 C with 5% CO2. The cells were then stained for 1 hour with crystal violet/5%
formaldehyde and washed 3 times with deionized water. The plates were air dried and the numbers of plaques in each well manually counted. Alternatively, other methods, such as e.g. TCID50 may be applied.
Table 3. Design of schedule and longevity experiments, 10 mice/group;
Immunization schedule as for Table 2, but in addition; interim bleeds 2, 6, 10, 14, 18 and 22 weeks after second immunization; end-bleed 26 weeks after second immunization; only with the preferred dose; only subcutaneous route;
number of experiments: 1. For experimentation purposes, the Thl adjuvant was added directly to the SARS-CoV-2/alum formulation before immunization of the mice.
Adjuvants (mice/group) Alum+
Route w/o adjuvant Alum Thl adjuvant Vaccine s.c 20 20 20 Placebo, s.c. 20 20 20 Protective capacity. The protective capacity of inactivated SARS-CoV-2 is assessed using a SARS-susceptible transgenic mouse expressing a humanized ACE2 protein (Jackson Laboratory) (Tseng, C.-T.K. et at., Severe Acute Respiratory Syndrome Coronavirus Infection of Mice Transgenic for the Human Angiotensin-Converting Enzyme 2 Virus Receptor (2007) J of Virol 81:1162-1173) or a NHP
model developed for SARS-CoV-2 infection. Groups of animals are immunized subcutaneously (s.c.) with different dosages of inactivated SARS-CoV-2 with or without adjuvant or PBS as a negative control. Three weeks after the last dose, animals are challenged with SARS-CoV-2 and monitored for disease progression and survival. In addition, serum samples are taken in order to determine the neutralizing antibody titers induced by vaccination in a PRNT assay.
Table 3A. Design of dosing experiment 4743 using SARS-CoV-2 ELISA-determined dosages.

Material SGP rVSB
Buffer PBS
AU/mouse 3.0 1.2 0.3 A13 /mouse 17 f.tg Immunization DO/D21 Bleeds D28/D35 Experiment 4743 Protocol Female Balb/c mice (10 mice/group) were immunized two times s.c. (100 L) on days 0 and 21 with doses and adjuvants as outlined in Table 3A. The readouts from the experiment were total IgG and subclasses (IgG1/IgG2a) and virus neutralization (PRNT). Vaccine formulation used in experiment 4743: purified inactivated SARS-CoV-2 produced from a research virus seed bank (rVSB) formulated in PBS with 17 fig A13+ (alum)/dose.
Antibody response to SARS-CoV-2 proteins. The immune responses in mice for the different doses and adjuvant formulations were assessed with a total IgG ELISA (Figure 4).
Plates were coated with either the S1 part (Figure 4A) or receptor binding domain (RBD) (Figure 4B) of the spike glycoprotein or the nucleoprotein (Figure 4C). Sera taken on days 28 and 35 were analyzed.
Plates were coated with 2 i_tg/mL antigen (Si, RBD and N protein) and mouse sera were tested at a starting dilution of 1:50 in 4-fold dilutions. For detection a secondary monoclonal antibody (HRP-conjugated goat anti-mouse IgG) was used and developed with ABTS and read at absorbance 405 nm. Wells were washed with PBS-T between each step. Endpoint titers were determined with a cut-offset to 3-fold the blank.
IgG subclass immune response. Plates were coated with the Si part (Figure 4A) of spike glycoprotein and sera taken on day 35 were analyzed. Subclass specific secondary antibodies (igG1 and IgG2a) conjugated with HRP were used for detection. As standard curves (4-paramater regression) for determination of the amount of the different IgG subclasses (IgG1 and IgG2a), monoclonal antibodies with different subclasses were used (IgG1 mAb clone 43 and IgG2a mAb clone CR3022). Bound HRP-conjugated secondary mAbs were developed with ABTS and read at absorbance 405 nm. Wells were washed with PBS-T between each step. The relative IgG subclass concentration is shown in Figure 5A
and the ratio of IgG2a/IgG1 in Figure 5B.
Observations from Experiment 4743. Inactivated SARS-CoV-2 formulated with alum induced antibodies in mice against SARS-CoV-2 detected by ELISA measuring antibodies to SI protein, receptor binding domain (RBD) and nucleocapsid protein (N) (Fig. 4A-C). An increase in immunogenicity was observed between bleeds on day 28 and day 35. In groups receiving the lowest dose (0.3 AU), a smaller increase not significantly above the placebo was seen for Si and RBD ELISA
titers.

The alum-adjuvanted inactivated SARS-CoV-2, as expected, promoted an immune response shifted more towards a Th2 (IgG1) compared with a Thl (IgG2a) response as demonstrated by quantification of IgG subclasses by Si ELISA. The total amounts of IgG2a and IgG1 measured and the ratio of IgG2a:IgG1 in the treatment groups are shown in Figs. 5A and 5B, respectively.
A shift in the immune response toward Th1 (IgG2a) would likewise be expected by addition of a Thl-stimulating adjuvant to the SARS-CoV-2 vaccine composition.
Further immunization experiments are carried out in mice using GMP material with low doses (3, 1.2 and 0.3 AU) as a bridge between research and GMP material, as well as analyses of GMP material in mice with human doses (40, 10 and 3 AU).
Additionally, a challenge study is carried out in immunized non-human primates (NI-IP) (see Figure 8) and a passive transfer study is carried out in hamsters using sera from human subjects vaccinated with the SARS-CoV-2 vaccine candidate of the invention (see Table lc).
Table lc. Passive transfer study of the SARS-CoV-2 vaccine candidate of the invention in hamsters.
Study objective: Proof of concept that the SARS-CoV-2 vaccine candidate of the invention induces neutralizing antibodies providing protection against SARS-CoV-2 challenge in an animal model Study design: Syrian hamsters receive sera from vaccinated subjects of the SARS-CoV-2 vaccine candidate of the invention Phase 1/2 study (see Example 4 below).
Hamsters are then challenged intranasally with SARS-CoV-2, Victoria/1/2020 A 10 day follow up includes:
Clinical observations and body weights recorded daily Viral shedding/viral loads determined via RT-qPCR
Circulating antibodies prior to challenge (neutralization) Tissues (lung and upper respiratory tract) taken at necropsy for determination of viral load and for histology Example 3. Testing of SARS-CoV-2 vaccine for antibody-dependent enhancement (ADE) of disease and immunopathology Although the mechanism is poorly understood, antibodies produced in response to a previous coronavirus infection or vaccination can increase the risk for 1) immunopathology and/or 2) antibody-dependent enhancement of disease (ADE) during subsequent coronavirus infection(s). As such, any stimulation of antibodies to SARS-CoV-2 presents a hypothetical risk. In this regard, several approaches are undertaken to ensure safety of the current vaccine.
hi vitro antibody-dependent enhancement assays. Immune sera from inactivated SARS-CoV-2-vaccinated mice are assessed for hallmarks of enhanced disease in vitro. Such assays are described by e.g. Wang, S.-F., et at. 2014 (Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins (2014) BBRC 451:208-214). Briefly, susceptible cell types or cell lines are incubated with immune sera and subsequently infected with SARS-CoV-2.
Cells are assessed for cytopathic effect and/or production of inflammatory markers.
Mouse model of immunopathology. The risk of vaccine-enhanced immunopathology on challenge is assessed in a Balb/c mouse model as described by Tseng C.T. et at.
(Immunization with SARS
Coronavirus Vaccines Leads to Pulmonary lmmunopathology on Challenge with the SARS Virus (2012) PLoS ONE 7(4):e35421). Briefly, the mice are immunized twice at two-week intervals with inactivated SARS-Cov-2 formulated as described herein followed by challenge with SARS-CoV-2 SARS-CoV-2 titers and immune cell infiltration of the lung are tested.
Non-human primate model of ADE. The risk of ADE development in non-human primates is assessed as described by Luo F, et at. (Evaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV Vaccine (2018) Virologica Sin/ca 33:201-204). Briefly, NHPs are immunized with inactivated SARS-CoV-2, followed by SARS-CoV-2 challenge and evaluation of symptoms and disease pathology.
Example 4. Clinical Phase 1 study Formulation of inactivated SARS-CoV-2 for Phase I trial. The objective of the Phase 1 trial is to assess the safety of the vaccine, along with immunogenicity, and to determine an optimal dose and adjuvant(s). As such, three antigen doses are tested in clinical phase 1:
High, Medium and Low, which are chosen to have a distance between each dose of approximately 3-fold and a span covering about a 10-fold difference between the high and low doses. The dose range is selected in part to indicate any potential dose-sparing effect of a Thl adjuvant.
The SARS-CoV-2 virus as purified herein has a high purity of >90% as assessed by SDS-PAGE, SE-HPLC and/or SARS-CoV-2 ELISA (data not shown). Furthermore, preliminary studies have indicated that the incidence of genetic heterogeneities during passage of the virus is low and no particular individual mutations stand out (data not shown).
The SARS-CoV-2 virus as purified herein has a high purity of >90% as assessed by SDS-PAGE, SE-HPLC and/or SARS-CoV-2 ELISA (see, e.g., Fig. 7). Furthermore, preliminary studies have indicated that the incidence of genetic heterogeneities during passage of the virus is low and no particular individual mutations stand out (data not shown).
To arrive at a dose range, the SARS-CoV-2 virus was compared with JEV, specifically assessing SE-HPLC peak area per dose equivalent (recorded as milli-absorption units x minutes; mAU), the total amount of inactivated viral particles per dose and the total viral surface equivalent per dose (see Table 4). This assessment was based on the assumption of a similar surface antigen density between S (spike;
SARS-CoV-2) and E (envelope; JEV) proteins. Total protein was determined by iii.BCA assay (Table 4). Although the assay was variable, a correspondence of 1 mAU to ยจ2 ug total protein per mL was observed. Another determination using an optimized SARS-CoV-2 S-protein ELISA, as outlined in Example 1, was also performed.
Table 4. Comparison of JEV and SARS-CoV-2 quantification parameters and total protein in Low, Medium and High SARS-CoV-2 dosage groups.
Ratio total Ratio surface Estimated total SE-HPLC peak particle antigen SARS-CoV-2 area equivalent equivalent equivalent protein/dose in Dose CoV/JEV CoV/JEV CoV/JEV lag (u.BCA assay) Low 0.25 0.015 0.070 0.5 Medium 1 0.058 0.288 2 High 2.5 0.145 0.719 5 As SARS-CoV-2 virus particles (-92 nm diameter) are much larger than Flavivirus particles (-40 nm), corresponding to an approximately 5-fold greater virus surface area per particle, an equivalently higher antigen content is expected. Furthermore, other inactivated virus vaccine preparations, including JEV
(IXIAR0), TBE (Enccpur) and HcpA (VAQTA) reported antigen doses in the low ng to ng protein range. As these viruses are all formalin inactivated, the BPL-inactivated SARS-CoV-2 virus of the current invention has better preserved surface antigen proteins, i.e., a better quality antigen, and requires a lower total protein dose.
For entry into the clinic a further antigen determination assay (SARS-CoV-2 ELISA assay as described in Example 1) was developed and the doses of the vaccine formulations for entry into Phase 1 trials were determined using this assay. The Phase 1 treatment groups are set forth in Table 5.
Formulation of SARS-CoV-2 vaccine pr phase I trial (0.5 mL/dose,):
-Antigen (inactivated SARS-CoV-2) target doses:
Low: 3 AU/0.5 mL (6 AU/mL)*
Medium: 10 AU/0.5 mL (20 AU/mL) High: 40 AU/0.5 mL (80 AU/mL) *doses determined by the SARS-CoV-2 ELISA assay as described in Example 1 -Aluminium hydroxide (A13+): 0.5 mg/dose (1 mg/mL) -Thl adjuvant -Recombinant Human Serum Albumin (rHSA): ยจ25 ug/dose (-50 ps/mL) -Buffer: Phosphate buffered saline (PBS) In some cases, vaccinated subjects are challenged with an infectious dose of live SARS-CoV-2 virus (Asian and/or European lineage).
Table 5. Treatment groups for Phase 1 testing of inactivated SARS-CoV-2 vaccine (low, medium and high doses are those provided in Table 4).
Group Antigen Aluminium Thl adjuvant hydroxide 1 Low 2 Med 3 High 7 Low -1 -1 8 Med -1 -1 9 High Example 5. Testing of Sera of vaccinated organism with a neutralization assay Sera of vaccinated mice, hamsters, non-human primates or humans can be tested in neutralization assays such as e.g. described in "Szurgot, I., Hanke, L., Sheward, D.J. et al.
DNA-launched RNA
replicon vaccines induce potent anti-SARS-CoV-2 immune responses in mice. Sci Rep 11, 3125 (2021). https://doi.org/10.1038/s41598-021-82498-5".
The read-out of the test gives an indication how well sera of vaccinated subjects can neutralize new variants and thus guides in the design of the vaccine.
Example 6. Liquid chromatography with tandem mass spectrometry (LC-MS-MS)analysis of inactivated SARS-CoV-2 Methodology:

Two samples were separated using SDS-polyacrylamide gel electrophoresis and the bands were visualized by silver staining. The bands were cut and subjected to in-gel digestion with trypsin and the resulting peptides analysed with nano-liquid chromatography coupled to a high-resolution accurate mass spectrometer. Peptides were identified from raw spectra using the MaxQuant software package and the UniProt reference databases for SARS-CoV-2 and Chlorocebus sabaeus. To account for modifications the data were re-searched specifically for 13-propiolactone modifications, and the obtained results were confirmed with a second independent search algorithm (Sequest in Proteome Discoverer suite). Additionally, data were searched with the FragPipe package to account for further unknown MS-detectable modifications.
Results:
Protein identification:
The bands could be clearly attributed to the three main viral proteins (Spike-protein, Membrane-protein, Nucleoprotein) as well as to background proteins from the host system (see Figure 10).
Traces of SARS-CoV-2 ORF9b and the replicase polyprotein could also be detected, but these proteins were probably not well resolved on the gel due to their size. The separation pattern on the gel was very similar for both samples with the exception of a host protein band (band 2.3), a slightly different S-protein pattern (bands 2.10-2.13), and an expected strong band of serum albumin in one of the samples (sample 2). Additionally, a number of typical lab contaminants of human origin (e.g.
keratins) were detected in the background of both samples. The processing of the Spike-protein (from full length to Sl, S2, and S2') is difficult to resolve with the applied methodology but is most likely represented by the pattern in bands 9-13 in both samples.
Modification analysis:
Based on a publication by Uittenbogaard et al. (Reactions of13-Propiolactone with Nucleobase Analogues, Nucleosides, and Peptides, Protein Structure and Folding l Volume 286, ISSUE 42, P36198-36214, October 21, 2011), it was expected to find B-propiolactone (BPL) modifications on cysteine, methionine, and histidine. Uittenbogaard et al. studied amino acids which are subject to modification by beta-propiolactone, along with the type of modification, e.g., acylation, alkylation.
They have shown that BPL can react with up to 9 different amino acids (C,H,M,D,E,Y,K,E,S) depending on actual pH. In their studies higher conversions within the relevant pH range 7 to 9 were observed for Cysteine (>95%), Histidine (15-25%) and Methionine (36%) residues. The conversion rates for Aspartic Acid, Glutamic acid and Tyrosine were much lower in the range of approximately 3-15%. It was shown that disulfide groups in Cystine residues do not react.

In BPL-inactivated SARS-CoV-2 particles, BPL modifications could be detected (mainly in the form of +72 Da) but at a low abundance. Out of 2894 (sample 1) and 3086 (sample 2) identified spectra for SARS-CoV-2 proteins only 73 and 110, respectively, carried a BPL modification, which translates to 2.5 to 3.6 % (see Table 6). This was also confirmed by the open modification search using FragPipe, which attributed a similarly low fraction of spectra to mass differences matching the BPL-modification.
Table 6. Number of identified SARS-CoV-2 peptide spectra Sample Total spectra BPL spectra % modified Sample 1 2894 73 2.5%
Sample 2 3086 110 3.6%
Spectra of all BPL-modified peptides reported for SARS-CoV-2 proteins were inspected manually of which 6 to 8 sites were confirmed for sample 1 and 2, respectively (see Table 6). For all of these validated sites also the unmodified peptides were identified suggesting that the modification with BPL
never reached 100%. We estimated the degree of modification on a particular site (the so-called site occupancy) as the ratio of modified to unmodified peptide for the same modification site normalized to the protein abundance for each band. We then selected the maximum occupancy for each site as a conservative measure of the degree of site modification. As shown in Table 7 the occupancy was in general rather low for the sites identified, in agreement with the total number of identified spectra.
The only exception, M234 of the nucleoprotein, has to be interpreted carefully, as that particular peptide sequence has problematic features which likely make the estimation for this particular peptide less accurate and reliable as compared to the other sites.
Table 7. BPL-modified sites identified and their occupancy Protein Site Position % occupancy sample 1 %
occupancy sample 2 Spike-protein H207 <0.1% 16%
Spike-protein H245 1% 3%
Spike-protein C379 <0.1% n.d.
Spike-protein M1029 <0.1% <0.1%
Spike-Protein C1032 <0.1% n.d.
Membrane protein H154 <0.1% <0.1%
Membrane protein H155 1% 1%
Membrane protein C159 n.d. <0.1%

Membrane protein 1-1210 5% 6%
Nucleoprotein M234 <0.1% 88%*
n.q. = not quantified; n.d. = not detected *quantification uncertain, due to missed cleavages and oxidation Apart from the expected modifications the FragPipe search revealed two other modifications (most likely acetaldehyde and acetylation) to occur in around 10% of the spectra.
These modifications represent most likely artifacts introduced during gel staining and sample preparation, as they also occur on contaminant proteins.
Summary:
Based on the results described above it is concluded that the main components in these samples corresponds to SARS-CoV2 proteins. The BPL modifications were detectable but appeared to be low, i.e. around 3% on whole SARS-CoV-2 proteome level (i.e. all SARS-CoV-2 proteins identified).
Only 5 amino acids of the S-protein were found to be modified and this was also only detected for a minority of the analysed S-protein (e.g. around 16% for the Spike-protein at the H207 amino acids, i_e the probability to have a modification at H207 was around 16%). The two samples differ only slightly with respect to some background proteins and in their degree of modification, with sample 1 showing slightly lower levels of BPL-modification. Please note that only about 30 to 40% of the amino acids of the Spike protein could be tested.
Conclusion:
This data supports the view that the mild inactivation approach of the invention minimizes the modifications within the S-protein and thus the native surface of the S-protein is largely preserved.
In comparison, determination of modifications by BPL inactivation of flu samples were more frequent, i.e. 83 sites on HA and 43 sites on NA for one sample flu vaccine (NIBRG-121xp) and 99 sites on HA and 39 sites on NA for another sample (NYMC-X181A) were modified, wherein HA and NA are the two major membrane glycoproteins, i.e. the primary immunogens for flu (She Yi-Min et al., Surface modifications of influenza proteins upon virus inactivation by beta-propiolactone;
Proteornics 2013, 13, 3537-3547, DOI 10.1002/pmic.201300096). Thus BPL
inactivation of influenza virus can lead to numerous protein modifications including some affecting membrane fusion.
Example 7. Further liquid chromatography with tandem mass spectrometry (LC-MSMS) analysis of inactivated SARS-CoV-2 Methodology:
A further LC-MSMS analysis of BPL-inactivated SARS-CoV-2 particles, as described in Example 6, was performed in order to obtain greater coverage of the proteins. Five aliquots of the BPL-inactivated SARS-CoV-2 sample were separated on SDS-PAGE and the bands visualized by either silver staining for visualization or Coomassie staining for processing. The Coomassie-stained bands corresponding to spike protein (based on previous analysis) were subjected to in-gel digestion with trypsin or chymotrypsin or to acid hydrolysis. Trypsin digests were performed twice, once with and once without previous PNGase F (peptide:N-glycosidase F) digestion, to identify peptides masked by glycosylation.
Digested peptides were analysed by LC-MSMS essentially as described in Example 6. In particular, the resulting peptides were analyzed with nano-liquid chromatography coupled to a high-resolution accurate mass spectrometer. Peptides were identified from raw spectra using the MaxQuant software package and the UniProt reference databases for SARS-CoV-2 and Chlorocebus sabaeus in combination with a database of common lab contaminants. To account for modifications the data were also searched specifically for fl-propiolactone (BPL) modifications, and spectra of all BPL-modified peptides of the SARS-CoV-2 spike protein were manually validated. The degree of modification was globally estimated as the percentage of BPL-modified spectra identified, and on site-level by calculating site occupancies from the ratio of modified to unmodified peptides for each peptide/site separately.
Results:
The total coverage of particular SARS-CoV-2 proteins, using the combination of four digestion methods (i.e. (i) trypsin (ii) trypsin + PNGase F (iii) chymotrypsin and (iv) acid hydrolysis) was as follows:
Spike (S) protein ยจ 91.5%
Membrane (M) protein ยจ 60.36%
Nucleoprotein (N) ยจ 74.70%
The number of BPL-modified peptides in the inactivated SARS-CoV-2 particles, based on each digestion method, is shown in Table 8 below:
Table 8: Number of identified SARS-CoV-2 peptide spectra across all bands analyzed Sample Total BPI, % BPI, modified modified Trypsin 3148 97 3.1%
Ttypsin + PNGase 2354 61 2.6%
Chymotrypsin 2753 174 6.3%
Acid hydrolysis 939 33 3.5%
Total 9194 365 4.0%
As shown in Example 6, this confirms that the percentage of BPL-modificd peptides is low regardless of the digestion method, e.g. less than 7%, 2 to 7% or around 2-5% on average.
Using a combination of the four digestion methods described above, a greater coverage of amino acid residues in SARS-CoV-2 proteins could be achieved. Accordingly, BPL-modifications were detected att the positions in the spike (S) and membrane (M) proteins shown in Table 9 below. The mean percentage occupancy at each site, as described in Example 6 above, is also shown in Table 9.
Table 9. BPL-modified sites identified in S protein and their occupancy Protein Site Position (1/0 occupancy Spike-protein H49 1%
Spike-protein H146 2%
Spike-protein C166 1%
Spike-protein M177 6%
Spike-Protein H207 1%
Spike-protein H245 13%
Spike-protein C432 8%
Spike-protein H519 2%
Spike-protein H625 7%
Spike-Protein M1029 2%
Spike-Protein H1058 11%
Spike-protein H1083 3%
Spike-protein H1088 4%
Spike-protein H1101 1%
Spike-protein H1159 4%

Spike-Protein H1271 1%
Membrane protein H125 <10%
Membrane protein H154 <10%
Membrane protein H155 <10%
Membrane protein H210 <10%
From the data in Table 9, it can be seen that up to around 16 residues in the spike (S) protein may be modified, and up to 4 residues in the membrane (M) protein. The occupancy at each site is low, e.g.
less than 20%, typically less than 10%. Therefore the inactivated SARS-CoV-2 particles show a low degree of BPL-modifications.

ADDITIONAL ASPECTS OF THE INVENTION
In further aspects, the present invention provides:
Al. A SARS-CoV-2 vaccine comprising an optimally (e.g. wherein the native surface of the S-protein is preserved) inactivated SARS-CoV-2 particle, wherein the SARS-CoV-2 particle is able to seroconvert a subject that is administered the SARS-CoV-2 vaccine with at least a 70% probability.
A2. The SARS-CoV-2 vaccine of aspect Al, wherein the SARS-CoV-2 particle is able to serocovert the subject that is administered the SARS-CoV-2 vaccine with at least a 80%, 85%, 90%, or 95% probability.
A3. The vaccine of aspect Al or A2, wherein the SARS-CoV-2 particle has a RNA genome corresponding to the DNA sequence provided by any one of the nucleic acid sequences of = SEQ ID NO: 1 (see Genbank NC_045512.2), or a variant nucleic acid sequence that is at least 85% identical to SEQ ID NO: 1 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 9 (see NCBI MT066156), or a variant nucleic acid sequence that is at least 85%
identical to SEQ ID NO: 1 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 18 (see NCBI MVV598408). or a variant nucleic acid sequence that is at least 85% identical to SEQ ID NO: 18 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 20 (see NCBI MW520923). or a variant nucleic acid sequence that is at least 85% identical to SEQ ID NO: 20 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 22 (see NCBI MW422256). or a variant nucleic acid sequence that is at least 85% identical to SEQ ID NO: 22 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 24 (see NCBI MW493681). or a variant nucleic acid sequence that is at least 85% identical to SEQ ID NO: 24 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 26 (see NCBI MW306426). or a variant nucleic acid sequence that is at least 85% identical to SEQ ID NO: 26 and able to pack a virulent SARS-CoV-2.
A4. The vaccine of any one of aspects A1-A3, wherein the SARS-CoV-2 particle has an S protein as defined by the amino acid sequence = SEQ ID NO: 3, or a variant amino acid sequence that is at least 95%
identical to SEQ ID NO:
3 and able to pack a virulent SARS-CoV-2; or = SEQ Ti) NO: 11, or a variant amino acid sequence that is at least 95%
identical to SEQ ID
NO: 11 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 19, or a variant amino acid sequence that is at least 95%
identical to SEQ ID
NO: 19 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 21, or a variant amino acid sequence that is at least 95%
identical to SEQ ID
NO: 21 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 23, or a variant amino acid sequence that is at least 95%
identical to SEQ ID
NO: 23 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 25, or a variant amino acid sequence that is at least 95%
identical to SEQ ID
NO: 25 and able to pack a virulent SARS-CoV-2; or = SEQ ID NO: 27, or a variant amino acid sequence that is at least 95%
identical to SEQ ID
NO: 27 and able to pack a virulent SARS-CoV-2.
A4.1 The vaccine of any one of aspects Al -A4, comprising a second SARS-CoV-2 particle that is different to the first SARS-CoV-2 particle and is selected from the group consisting of SEQ ID NO: 1, 9, 18, 20, 22, 24 and 26.
AS. The vaccine of any one of aspects A1-A4 and A4.1, wherein the SARS-CoV-2 is inactivated by chemical inactivation, thermal inactivation, pH inactivation, or UV
inactivation or radiation inactivation.
A6. The vaccine of aspect AS, wherein the chemical inactivation comprises contacting the SARS-CoV-2 particles with a chemical inactivation agent for longer than is required to completely inactivate the SARS-CoV-2 as measured by plaque assay or as measured by plaque assay plus one day.
A7. The vaccine of aspect A6, wherein the chemical inactivation comprises contacting the SARS-CoV-2 particle with formaldehyde and/or beta-propiolactone, preferably beta-propiolactone.
AS. The vaccine of aspect A7, wherein the formaldehyde and/or beta-propiolactone inactivation comprises contacting the SARS-CoV-2 particle with formaldehyde and/or beta-propiolactone for between 2-10 days.
A9. The vaccine of any one of aspects A5-A8, wherein the chemical activation is performed at about 4 C or about 22 C.

A10. The vaccine of any one of aspects A1-A9, further comprising an adjuvant.
All. The vaccine of aspect A10, wherein the adjuvant is an aluminium salt adjuvant, optionally in combination with AS01, AS03, MF59, imiquimod and/or CpG 1018.
Al2. The vaccine of aspect All, wherein the aluminium salt adjuvant is aluminium hydroxide or aluminium phosphate salt.
A13. The vaccine of any one of A10-Al2, wherein the vaccine comprises or further comprises an adjuvant comprising a peptide and a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN).
A14. The vaccine of aspect A13, wherein the peptide comprises the sequence KLKL5KLK (SEQ
ID NO: 5) and the I-ODN comprises oligo-d(IC)13 (SEQ ID NO: 6).
A15. The vaccine of any one of aspects A1-A14, further comprising one or more pharmaceutically acceptable excipient.
Bl. A kit comprising a SARS-CoV-2 vaccine of any one of aspects Al-A15.
B2. The kit of aspect Bl, further comprising a second vaccine.
B3. The kit of aspect B2, wherein the second vaccine is another SARS-CoV-2 virus vaccine (e.g.
of another technology such as mRNA or adenovirus vectored), an influenza virus vaccine or a Chikungunya virus vaccine.
Cl. A method, comprising administering a first dose of a therapeutically effective amount of the SARS-CoV-2 vaccine of any one of aspects A1-A15 to a subject in need thereof.
C2. The method of aspect Cl, further comprising administering a second dose of a therapeutically effective amount of the SARS-CoV-2 vaccine.

C3. The method of aspect Cl or C2, wherein the second dose of the SARS-CoV-2 vaccine is administered about 7 days after the first dose of the SARS-CoV-2 vaccine.
C4. The method of aspect Cl or C2, wherein the second dose of the SARS-CoV-2 vaccine is administered about 14 days after the first dose of the SARS-CoV-2 vaccine.
C5. The method of aspect Cl or C2, wherein the second dose of the SARS-CoV-2 vaccine is administered about 21 days after the first dose of the SARS-CoV-2 vaccine.
C6. The method of aspect Cl or C2, wherein the second dose of the SARS-CoV-2 vaccine is administered about 28 days after the first dose of the SARS-CoV-2 vaccine.
C7. The method of any one of aspects C1-05, wherein the administering results in production of SARS-CoV-2 neutralizing antibodies.
Dl. A method of producing a SARS-CoV-2 vaccine, comprising (i) passaging a SARS-CoV-2 on Vero cells, thereby producing a culture medium comprising the SARS-CoV-2;
(ii) harvesting the culture medium of (i);
(iii) precipitating the harvested culture medium of (ii), thereby producing a SARS-CoV-2 supernatant; and (iv) optimally inactivating the SARS-CoV-2 in the SARS-CoV-2 supernatant of (iii) thereby producing an inactivated SARS-CoV-2.
D2. The method of aspect D1, further comprising concentrating the culture medium of (ii) prior to step (iii).
D3. The method of aspect D1 or D2, wherein the precipitation of (iii) comprises contacting the culture medium of (ii) with protamine sulfate or benzonase.
D4. The method of any one of aspects D1-D3, further comprising (v) dialyzing the inactivated SARS-CoV-2 of (iv), thereby producing a dialyzed SARS-CoV-2.

D5. The method of aspect D4, further comprising a step (vi), comprising filtering the dialyzed SARS-CoV-2 of (v).
D6. The method of any one of aspects D1-D5, wherein the inactivating is by chemical inactivation, thermal inactivation, pH inactivation, or UV inactivation.
D7. The method of aspect D6, wherein the chemical inactivation comprises contacting the SARS-CoV-2 particle with a chemical inactivation agent for at least 4 days.
D8. The method of aspect D6 or D7, wherein the chemical inactivation agent comprises formaldehyde.
D9. The method of any one of aspects D6-D8, wherein the chemical activation is performed at about 4 C or about 22 C.
D10. The method of aspect D8 or D9, further comprising neutralizing the formaldehyde.
D11. The method of aspect D10, wherein the neutralizing is performed with sodium metabisulfite.
D12. The method of any one of aspects Dl-D11, wherein the chemical inactivation is performed with BPL, preferably at a concentration of 300 to 700ppm, more preferably 500ppm and inactivated for about 1 to 48h, preferably 20 to 28h, most preferred 24 hours 2 hours (such as also 1 hour or 0.5 hour) at 2 C to 8 C.
D13. The method of aspect D12, wherein the chemical inactivation is followed by a hydrolization step for 2.5 hours 0.5 hours at 35 C to 39 C, preferably around 37 C.
E 1 . The use of the optimally inactivated SARS-CoV-2 vaccine of any one of aspects Al-A15 for the treatment and/or prevention of a SARS-CoV-2 infection.
E2. The use of aspect El, wherein the inactivated SARS-CoV-2 vaccine is administered in a first dose of a therapeutically effective amount to a subject in need thereof E3. The use of aspect E2, wherein the inactivated SARS-CoV-2 vaccine is administered in a second dose of a therapeutically effective amount to the subject.
E4. The use of aspect E3, wherein the second dose of the inactivated SARS-CoV-2 vaccine is administered about 7 days after the first dose of the SARS-CoV-2 vaccine.
E5. The use of aspect E3, wherein the second dose of the SARS-CoV-2 vaccine is administered about 14 days after the first dose of the SARS-CoV-2 vaccine.
E6. The use of aspect E3, wherein the second dose of the SARS-CoV-2 vaccine is administered about 21 days after the first dose of the SARS-CoV-2 vaccine.
E7. The usc of aspect E3, wherein the second dose of the SARS-CoV-2 vaccine is administered about 28 days after the first dose of the SARS-CoV-2 vaccine.
E8. The use of any one of aspects E1-E6, wherein the administering results in production of SARS-CoV-2 neutralizing antibodies.
Fl. A pharmaceutical composition for use in the treatment and prevention of a SARS-CoV-2 infection, wherein said pharmaceutical composition comprises the optimally inactivated SARS-CoV-2 vaccine of any one of aspects A 1-A15.
F2. The pharmaceutical composition of aspect Fl, wherein the inactivated SARS-CoV-2 vaccine is administered in a first dose of a therapeutically effective amount to a subject in need thereof F3. The use of aspect F2, wherein the inactivated SARS-CoV-2 vaccine is administered in a second dose of a therapeutically effective amount to the subject.
F4. The use of aspect F3, wherein the second dose of the inactivated SARS-CoV-2 vaccine is administered about 7 days after the first dose of the SARS-CoV-2 vaccine.
F5. The use of aspect F3, wherein the second dose of the SARS-CoV-2 vaccine is administered about 14 days after the first dose of the SARS-CoV-2 vaccine.

F6. The use of aspect F3, wherein the second dose of the SARS-CoV-2 vaccine is administered about 21 days after the first dose of the SARS-CoV-2 vaccine.
F7. The use of aspect F3, wherein the second dose of the SARS-CoV-2 vaccine is administered about 28 days after the first dose of the SARS-CoV-2 vaccine.
F8. The use of any one of aspects Fl-F6, wherein the administering results in production of SARS-CoV-2 neutralizing antibodies.
G1 . A SARS-CoV-2 vaccine comprising an effective amount of antigen, wherein said effective amount is able to seroconvert a subject that is administered the SARS-CoV-2 vaccine with at least a 70% probability.
G2. The SARS-CoV-2 vaccine according to aspect Gl, wherein said effective amount is able to seroconvert a subject that is administered the SARS-CoV-2 vaccine with at least 80%, 85%, 90%, or 95% probability.
G3. The SARS-CoV-2 vaccine according to aspect G1 or G2, wherein said effective amount is between about 1 to 100 AU/dose, preferably between about 2 to 75 AU/dose, preferably between about 3 and 60 AU/dose, more preferably between about 3 and 55 AU/dose, more preferably between about 3 and 53 AU/dose.
G4. The SARS-CoV-2 vaccine according to aspect G3, where said effective amount is determined by ELISA wherein the antigen units (AU) correspond to ACE-2 binding capacity of the spike protein used as a standard.
Hl. A SARS-CoV-2 vaccine comprising an inactivated SARS-CoV-2 particle;
wherein a native surface conformation of the SARS-CoV-2 particle is preserved in the vaccine, such that the vaccine is capable of generating neutralizing antibodies against native SARS-CoV-2 particles in a human subject.
H2. A SARS-CoV-2 vaccine according to aspect H1, wherein viral RNA in the inactivated SARS-CoV-2 particle is replication-deficient.

H3. A SARS-CoV-2 vaccine according to aspect HI or H2, wherein viral RNA in the inactivated SARS-CoV-2 particle (i) is alkylated and/or acylated (ii) comprises one or more modified purine (preferably guanine) residues or strand breaks and/or (iii) is cross-linked with one or more viral proteins.
H4. A SARS-CoV-2 vaccine according to any preceding aspect, wherein the inactivated SARS-CoV-2 particle is a beta-propiolactone-inactivated SARS-CoV-2 particle, preferably at a concentration of 300 to 700ppm, more preferably 500ppm and inactivated for about 1 to 48h, preferably 20 to 28h, most preferred 24 hours 2 hours (such as also 1 hour or 0.5 hour) at 2 C to 8 C, followed optionally by a hydrolyzation for 2.5 hours 0.5 hours at 35 C to 39 C, preferably around 37 C.
H5. A SARS-CoV-2 vaccine according to any preceding aspect, wherein the inactivated SARS-CoV-2 particle is an ultraviolet (UV)-inactivated SARS-CoV-2 particle.
H6. A SARS-CoV-2 vaccine according to any preceding aspect, wherein surface proteins in the inactivated SARS-CoV-2 particle comprise reduced modifications compared to viral RNA in the inactivated SARS-CoV-2 particle, preferably wherein surface proteins comprise a reduced proportion of modified residues compared to viral RNA in the inactivated SARS-CoV-2 particle;
said modifications being with respect to a native SARS-CoV-2 particles, preferably wherein said modifications comprise alkylated and/or acylated nucleotide or amino acid residues.
H7. A SARS-CoV-2 vaccine according to any preceding aspect, wherein the inactivated SARS-CoV-2 particle comprises a native conformation of (i) spike (S) protein; (ii) nucleocapsid (N) protein;
(iii) membrane (M) glycoprotein; and/or (iv) envelope (E) protein; preferably wherein the inactivated SARS-CoV-2 particle comprises a native conformation spike (S) protein.
H8. A SARS-CoV-2 vaccine according to any preceding aspect, wherein infectivity of mammalian cells by the inactivated SARS-CoV-2 particle is reduced by at least 99%, 99.99% or 99.9999%
compared a native SARS-CoV-2 particle, or wherein infectivity of mammalian cells by the inactivated A SARS-CoV-2 particle is undetectable.
H9. A SARS-CoV-2 vaccine according to any preceding aspect, further comprising one or more pharmaceutically acceptable excipients, such as e.g., human serum albumin (HSA).

H10. A SARS-CoV-2 vaccine according to any preceding aspect, further comprising an adjuvant.
H11. A SARS-CoV-2 vaccine according to aspect H10, wherein the adjuvant comprises aluminium hydroxide or aluminium phosphate.
H12. A SARS-CoV-2 vaccine according to aspect H11, wherein aluminium hydroxide or aluminium phosphate is the only adjuvant in the vaccine.
H13, A SARS-CoV-2 vaccine according to aspect H10 or 11, wherein the adjuvant comprises or further comprises a Thl response-directing adjuvant.
H14. A SARS-CoV-2 vaccine according to aspect H13, wherein the Thl response-directing adjuvant comprises 3-0-desacy1-4'-monophosphoryl lipid A (MPL), saponin QS-21, a CpG-containing oligodeoxynucleotide (CpG ODN), squalene, DL-a-tocopherol, a cationic peptide, a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN) and/or imiquimod.
His. A SARS-CoV-2 vaccine according to aspect H10, wherein the adjuvant comprises:
(i) a liposomal preparation comprising 3-0-desacy1-4'-monophosphoryl lipid A
(MPL) and saponin QS-21, preferably Adjuvant System 01;
(ii) a CpG ODN comprising the sequence S' TGACTGTGAACGTTCGAGATGA 3' (SEQ ID
NO:4), preferably CpG 1018;
(iii) squalene, DL-a-tocopherol and polysorbate 80 (preferably Adjuvant System 03);
(iv) an oil-in-water emulsion comprising squalene, Tween 80 and Span 85, preferably MF59;
(v) a peptide of sequence KLKL5KLK (SEQ ID NO: 5) and oligo-d(IC)13 (SEQ ID
NO: 6), preferably IC31; or (vi) an aluminium salt and optionally a Thl-directing adjuvant.
H16. The SARS-CoV-2 vaccine according to any preceding aspect, wherein the vaccine is able to seroconvert a subject that is administered the SARS-CoV-2 vaccine with at least a 70%
probability.

H17. The SARS-CoV-2 vaccine according to aspect H16, wherein the SARS-CoV-2 vaccine is able to seroconvert the subject that is administered the SARS-CoV-2 vaccine with at least an 80%. 85%, 90%, or 95% probability.
H18. The SARS-CoV-2 vaccine according to any one of the preceding aspects, wherein the SARS-CoV-2 particle comprises an RNA sequence (and/or fragments thereof, optionally comprising modified (preferably alkylated or acylated) nucleotide residues) corresponding to a DNA
sequence (i) as defined by SEQ ID NO: 9; or (ii) having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID NO: 9; preferably wherein a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence is able to pack a virulent SARS-CoV-2.
H19. The SARS-CoV-2 vaccine according to any one of the preceding aspects, wherein the said vaccine comprises an additional SARS-CoV-2 particle that comprises an RNA
sequence (and/or fragments thereof, optionally comprising modified (preferably alkylated or acylated) nucleotide residues) corresponding to a DNA sequence (i) as defined by SEQ ID NO: 18; or (ii) having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID
NO: 18; preferably wherein a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence is able to pack a virulent SARS-CoV-2.
H20. The SARS-CoV-2 vaccine according to any one of the preceding aspects, wherein the said vaccine comprises an additional SARS-CoV-2 particle that comprises an RNA
sequence (and/or fragments thereof, optionally comprising modified (preferably alkylated or acylated) nucleotide residues) corresponding to a DNA sequence (i) as defined by SEQ ID NO: 22; or (ii) having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID
NO: 22; preferably wherein a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence is able to pack a virulent SARS-CoV-2.
H21. The SARS-CoV-2 vaccine according to any preceding aspect, wherein the vaccine is obtained or obtainable from Vero cells.
H22. The SARS-CoV-2 vaccine according to any preceding aspect, wherein, upon administration to a human subject, the vaccine (i) does not induce antibody-dependent enhancement (ADE) of SARS-CoV-2-associated disease (COVID-19): and/or (ii) does not induce immunopathology in the subject.

H23. A method of preventing or treating SARS-CoV-2 infection and/or SARS-CoV-2-associated disease (COVID-19) in a human subject in need thereof, comprising administering a prophylactically or therapeutically effective amount of the SARS-CoV-2 vaccine of any preceding aspect to the subject.
H24. The method according to aspect H23, further comprising administering a second dose of a prophylactically or therapeutically effective amount of the SARS-CoV-2 vaccine, preferably wherein the second dose of the vaccine is the same formulation as the first.
H25. The method according to aspect H23 or H24, wherein said prophylactically or therapeutically effective amount of the SARS-CoV-2 vaccine per dose is defined as about 1 to 100 AU/dose, preferably between about 2 to 75 AU/dose, preferably between about 3 and 60 AU/dose, more preferably between about 3 and 55 AU/dose, more preferably between about 3 and 53 AU/dose, as assessed by ELISA, even more preferably between about 3 and 40 AU/dose such as e.g. 40 AU/dose.
H26. The method according to aspect H23 or 24, wherein said prophylactically or therapeutically effective amount per dose of the SARS-CoV-2 vaccine is defined as about 0.05 to 50 vig total 70 protein, about 0.1 to 25 vtg, about 0.25 to 12.5 vig, preferably about 0.5 to 5 jig total protein, as measured by (u)BCA.
H27. The method according to aspect H23 or H24, wherein said prophylactically or therapeutically effective amount per dose of the SARS-CoV-2 vaccine is defined as about 0.025 to 25 lag S-protein, about 0.05 to 12.5 lag, about 0.125 to 6.25 jig, preferably about 0.25 to 2.5 jig S-protein, as measured by ELISA.
H28. The method according to aspect H24, wherein the second dose of the SARS-CoV-2 vaccine is administered about 7 days, about 14 days, about 21 days, or about 28 days after a first dose of the SARS-CoV-2 vaccine, preferably wherein the second dose of the vaccine is the same formulation as the first.
H29. The method according to any one of aspects H22 to H28, wherein the administering results in production of SARS-CoV-2 neutralizing antibodies.

H30. A method of producing a SARS-CoV-2 vaccine, comprising:
(a) producing native SARS-CoV-2 particles;
(b) inactivating the native SARS-CoV-2 particles to obtain inactivated SARS-CoV-2 particles;
(c) incorporating the inactivated SARS-CoV-2 particles in a vaccine composition;
wherein a native surface conformation of the SARS-CoV-2 particle is preserved in the inactivation step, such that the vaccine is capable of generating neutralizing antibodies against native SARS-CoV-2 particles in a human subject.
H31. The method according to aspect H30, wherein the vaccine composition comprises aluminium hydroxide.
H32. The method according to aspect H31, wherein the SARS-CoV-2 vaccine comprising aluminium hydroxide contains less than 1.25 ppb Cu.
H33. The method according to aspect H32, wherein the inactivation step preferentially targets viral RNA in the SARS-CoV-2 particle.
H34. The method according to aspect H30 or H33, wherein the inactivation step comprises (i) alkylating and/or acylating viral RNA (ii) modifying purine (preferably guanine) residues or introducing strand breaks into viral RNA and/or (iii) cross-linking viral RNA
with one or more viral proteins.
H35. The method according to any one of aspects H30, H33 or H34, wherein the inactivation step comprises treating the native SARS-CoV-2 particles with beta-propiolactone.
H36. The method according to aspect H35, wherein a concentration of beta-propiolactone in the inactivation step is 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight, more preferably about 0.1% by weight.
H37. The method according to aspect H35 or H36, wherein the native SARS-CoV-2 particles are contacted with beta-propiolactone for at least 5 hours, at least 10 hours, at least 24 hour or at least 4 days.
H38. The method according to any of aspects H30 or H33 to H37, wherein the inactivation step is performed at about 0 C to about 25 C, preferably about 4 C or about 22 C.

H39. The method according to any of aspects H30 or H33 to H38, wherein the inactivation step comprises treating the native SARS-CoV-2 particles with ultraviolet (UV) light.
H40. The method according to any one of aspects H30 or H33 to H39, wherein step (a) comprises one or more of the following steps:
(i) passaging a SARS-CoV-2 on Vero cells, thereby producing a culture medium comprising the SARS-CoV-2;
(ii) harvesting the culture medium of (i);
(iii) precipitating the harvested culture medium of (ii), thereby producing native SARS-CoV-2 particles in a supernatant.
H41. The method according to aspect H40, further comprising concentrating the culture medium of (ii) prior to step (iii).
H42. The method according to aspect H40 or H41, wherein the precipitating of (iii) comprises contacting the culture medium of (ii) with protamine sulfate or benzonase.
H43. The method according to any one of aspects H30 or H33 to H42, further comprising dialyzing the inactivated SARS-CoV-2 particles, thereby producing a dialyzed SARS-CoV-2.
H44. The method according to aspect H43, further comprising filtering the dialyzed SARS-CoV-2.
H45. The method according to any one of aspects H30 or H33 to H44, wherein the inactivation step comprises contacting a liquid composition comprising native SARS-CoV-2 particles with a chemical viral inactivating agent in a container, mixing the chemical viral inactivating agent and the liquid composition comprising SARS-CoV-2 particles under conditions of laminar flow but not turbulent flow, and incubating the chemical viral inactivating agent and the liquid composition comprising SARS-CoV-2 particles for a time sufficient to inactivate the viral particles.
H46. The method according to aspect H45, wherein the inactivation step is performed in a flexible bioreactor bag.

H47. The method according to aspect H45 or H46, wherein the inactivation step comprises five or less container inversions during the period of inactivation.
H48. The method according to any one of aspects H45 to H47, wherein the mixing of the chemical viral inactivating agent and the composition comprising native SARS-CoV-2 particles comprises subjecting the container to rocking, rotation, orbital shaking, or oscillation for not more than 10 minutes at not more than 10 rpm during the period of incubation.
H49. The method according to any one of aspects H30 or H33 to H48, further comprising purifying the inactivated SARS-CoV-2 particles by one or more methods selected from (i) batch chromatography and/or (ii) sucrose density gradient centrifugation.
H50. The method according to any one of aspects H30 or H33 to H49, wherein step (c) comprises combining the inactivated SARS-CoV-2 particles with an adjuvant.
H51. The method according to aspect H50, wherein the adjuvant comprises a Thl response-directing adjuvant.
H52. The method according to aspect H50 or H51, wherein the adjuvant comprises 3-O-desacyl-4'-lipid A (MPL), saponin QS-21. a CpG-containing oligodeoxynucleotide (CpG
ODN), squalene, DL-a-tocopherol and/or imiquimod.
H53. A SARS-CoV-2 vaccine obtained or obtainable by the method of any one of aspects H30 or H33 to H52.
H54. Use of a SARS-CoV-2 vaccine of any one of aspects H1 to H22 or H53 for the treatment or prevention of a SARS-CoV-2 infection in a subject.
H55. A pharmaceutical composition for use in the prevention or treatment of a SARS-CoV-2 infection in a subject, wherein said pharmaceutical composition is the inactivated SARS-CoV-2 vaccine as defined in any one of aspects H1 to H22 or H53, optionally in combination with one or more pharmaceutically acceptable excipients and/or adjuvants.
H56. The SARS-CoV-2 vaccine as defined in any one of aspects H1 to H22 or H53 for use as a medicament.

H57. A vaccine, method, use or pharmaceutical composition according to any preceding aspect, wherein the subject is (i) an elderly subject, preferably a subject over 65, over 70 or over 80 years of age; (ii) an immunocompromised subject; or (iii) a pregnant subject.
H58. A vaccine, method, use or pharmaceutical composition according to any preceding aspect, for use in prevention or treatment of a SARS-CoV-2 infection without induction of (i) antibody-dependent enhancement (ADE) of SARS-CoV-2-associated disease (COV1D-19);
and/or (ii) immunopathology in the subject.
The present application claims priority from EP20168324.0 (06 Apr 2020), EP
20202118.4 (15 Oct 2020), EP 20211853.5 (04 Dec 2020) EP21154647.8 (01 Feb 2021), PCT/US2021/20313 (1-Mar-2021) and EP 21160913.6 (05 Mar 2021), the contents of which are incorporated herein by reference.
All publications mentioned in the above specification are herein incorporated by reference. Various modifications and variations of the described embodiments of the present invention will be apparent to those skilled in the art without departing from the scope and spirit of the present invention.
Although the present invention has been described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which arc obvious to thosc skilled in the art are intended to be within the scope of the following claims.

SEQUENCES
SEQ ID NO: 1 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate Wuhan-Hu-1, complete genome (GenBa nk: M N908947; Wu, F., et al. A new coronavirus associated with human respiratory disease in China (2020) Nature 579:265-269) ATTAAAGGTTTATACCTTCCCAGGTAACAAACCAACCAACTTTCGATCTCTTGTAGATCTGTTCTCTAAACGAACTTTA
AAA
TCTGTGTGG CTGTCACTCGGCTGCATGCTTAGTGCACTCACG
CAGTATAATTAATAACTAATTACTGTCGTTGACAG G ACA
CG AGTAACTCGTCTATCTTCTGCAGG CTGCTTACGGTTTCGTCCGTGTTGCAGCCG ATCATCAG CACATCTAG
GTTTCGTCC
GG GTG TG AC CG AAAG GTAAGATG G AG AG CCTTGTCCCTG G TTTCAACG AG AAAACACACG
TCCAACTCAG TTTG CCTG TT
TTACAGGTTCGCG ACGTG CTCG TACGTG G CTTTG G AG ACTCCGTG G AG GAG GTCTTATCAGAG
GCACGTCAACATCTTAA
AGATGG CACTTGTG GCTTAGTAGAAG TTGAAAAAG G CGTTTTG CCTCAACTTGAACAG CC CTATG
TGTTCATCAAACGTTC
GGATG CTCG AA CTG CACCTCATGGTCATGTTATG GTTG AG CTG GTAG CAGAACTCGAAG
GCATTCAGTACG GTCGTAGTG
GTGAGACACTTGGTGTCCTTGTCCCTCATGTGG G CG AAATACCAGTGGCTTACCG CAAG
GTTCTTCTTCGTAAG AACGGTA
ATAAAGG AG CTG GTGGCCATAGTTACG GCG CCGATCTAAAGTCATTTG ACTTAG GC GACG AG CTTG G
CACTG ATCCTTAT
GAAGATTTTCAAGAAAACTG G AA CACTAAACATAG CAGTG GTGTTACCCGTGAACTCATG C GTG AG
CTTAACGG AG GG G
CATACACTCG CTATGTCGATAACAACTTCTGTG G CC CTG ATG GCTACCCTCTTGAGTGCATTAAAG
ACCTTCTAG CACGTGC
TG GTAAAGCTTCATG CACTTTGTCCGAACAACTGGACTTTATTG ACACTAAG AG G G GTGTATACTG CTG
CCG TG AACATG A
GCATGAAATTGCTTG GTACACGG AACGTTCTG AAAAG AG CTATG AATTGCAGACACCTTTTG
AAATTAAATTG GCAAAGA
AATTTG A CAC CTTCAATG G G
GAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAG G GTTG A
AAAG AAAAAG CTTG ATG GCTTTATGG GTAG AATTCGATCTGTCTATCCAGTTGCG
TCACCAAATGAATGCAACCAAATGT
GCCTTTCAACTCTCATGAAGTGTG ATCATTGTG GTG AAACTTCATGGCAGACGGG CGATTTTGTTAAAG
CCACTTG CG AAT
TTTGTG G CACTG AG AATTTG ACTAAAG AAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTG
TTGTTAAAATTTATTG
TCCAGCATGTCACAATTCAG AAGTA G G AC CTG AG CATAGTCTTG CCGAATACCATAATG
AATCTGGCTTGAAAACCATTCT
TCGTAAG GGTG GTCGCACTATTG CCTTTG G AG GCTGTGTGTTCTCTTATGTTG G TTG
CCATAACAAGTGTG CCTATTG G GT
TCCACGTGCTAG CGCTAACATAGGTTGTAACCATACAG GTGTTGTTG GAG AAGGTTCCG AAG
GTCTTAATGACAACCTTCT
TG AAATACTC CAAAAAG AG AAAG TCAACATCAATATTGTTG GIG ACTTTAAA CTTAATG AAG AG
ATCGCCATTATTTTGGC
ATCTTTTTCTGCTTCCACAAGTG CTTTTGTGGAAACTGTGAAAGGTTTGG ATTATAAAG
CATTCAAACAAATTGTTG AATCC
TGTGGTAATTTTAAAGTTACAAAAG GAAAAG CTAAAAAAGGTGCCTG G
AATATTGGTGAACAGAAATCAATACTG AGTCC
TCTTTATGCATTTG CATCAG AG G CTG CTCGTGTTGTACG ATCAATTTTCTCCCGCACTCTTGAAACTG
CTCAAAATTCTGTGC
GTGTTTTACAGAAGGCCG CTATAACAATACTAG ATG GAATTTCACAGTATTCACTGAG ACTCATTG ATG
CTATGATGTTCA
CATCTG ATTTGGCTACTAACAATCTAG TTGTAATG G CCTACATTACAGGTGGTGTTGTTCAGTTG ACTTCG
CAGTGG CTAA
CTAACATCTTTG GCACTGTTTATG AAAAACTCAAACCCGTCCTTGATTGG CTTG AA G AG AAGTTTAAG G
AAG GTGTAGAGT
TTCTTAG AG AC G GTTG GG AAATTGTTAAATTTATCTCAACCTGTG CTTGTGAAATTGTCGGTGG
ACAAATTGTCACCTGTG
CAAAGGAAATTAAG GAG AGTG TTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGGCTTTGTGTG
CTGACTCTATCATTAT
TG GTG GAG CTAAACTTAAAG CCTTGAATTTAGGTG AAACATTTGTCACG CACTCAAAG GG ATTGTACAG
AAAGTGTG TTA
AATCCAG AG AAG AAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAG AG G G AG
AAACACTTCC CA
CAG AAGTGTTAACAG AG GAAGTTGTCTTG AAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTG AAG
CTGTTG AA
GCTCCATTGGTTG GTACACCAGTTTGTATTAACGGG CTTATGTTG
CTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTT
GCACCTAATATG ATGGTAACAAACAATACCTTCACACTCAAAG GCG GTG
CACCAACAAAGGTTACTTTTGGTGATG ACACT
GTGATAGAAGTGCAAGGTTACAAGAGTGTG AATATCACTTTTG AACTTGATG AAAG G
ATTGATAAAGTACTTAATG AG AA
GTGCTCTGCCTATACAGTTG AACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGG CAG AT G
CTGTCATAAAAACTTT
GCAACCAGTATCTGAATTACTTACACCACTGGG CATTG ATTTAGATGAGTGGAGTATG
GCTACATACTACTTATTTGATGA
GTCTGGTGAGTTTAAATTG G CTTCACATATGTATTG TTCTTTCTACCCT CCAG ATG AG GATG AAG
AAGAAGGTG ATTG TG A
AG AAG AAG AG TTTG AG CCATCAACTCAATATGAGTATG GTACTG AAGATGATTACCAAG
GTAAACCTTTGG AATTTG GTG
CCACTTCTGCTGCTCTTCAACCTGAAGAAG AG CAAGAAGAAGATTG GTTAGATG
ATGATAGTCAACAAACTGTTGGTCAA
CAAG ACGG CAGTG AG GACAATCAG ACAACTACTATTCAAACAATTGTTG AG GTTCAACCTCAATTAG AG
ATG GAACTTAC
ACCAGTTGTTCAG ACTATTG AAGTG AATAGTTTTAGTGGTTATTTAAAACTTACTG
ACAATGTATACATTAAAAATG CAG A
CATTGTG GAAG AAG CTAAAAAG GTAAAACCAACAGIGGTTGITAATGCAGCCAATGITTACCTTAAACATG
GAG G AG G T
GTTGCAG GAG CCTTAAATAAG G CTACTAACAATG CCATGCAAGTTGAATCTGATGATTACATAG
CTACTAATG GACCACTT
AAAGTGG GTG GTAGTTGTGTTTTAAGCGG ACACAATCTTG CTAAACACTGTCTTCATGTTGTC G G CC
CAAATG TTAACAAA
GGTGAAGACATTCAACTTCTTAAG AGTG CTTATGAAAATTTTAATCAG CAC GAAGTTCTACTTG
CACCATTATTATCAGCTG
GTATTTTTG GTG CTG AC CCTATACATTCTTTAAG AG TTTGTGTAG ATACTG TTCG
CACAAATGTCTACTTAG CTGTCTTTG AT
AAAAATCTCTATGACAAACTTGTTTCAAG CTTTTTG GAAATGAAG AG TG AAAAG CAAG
TTGAACAAAAGATCG CTG AG AT
TCCTAAAG AG G AAGTTAAGCCATTTATAACTGAAAGTAAACCTTCAGTTGAACAG AG AAAACAAG ATG
ATAAG AAAATCA

AAG CTTG TG TTG AAG AAG TTACAACAACT CT G G AAG AAACTAA G TT CCTCAC AG AAAACTT
G TTACTTT ATATTG ACATTA
ATG G CAATCTTCATCCAGATTCTG CCACT CTTG TTAG T G AC ATTG AC ATCA CTTT CTTAAAG
AAAG AT G CTCCATATATAGT
G G GTG ATG TTG TT CAAG AG G GTGTTTTAACTG CTGTG GTTATACCTACTAAAAAG G CTG GTG G
CACTACTG AAATG CTAG
CG AAAG CTTTG AG AAAA GTG CCAACAGACAATTATATAACCACTTACCCG G GTC AG G GTTTAAATG
GTTA CACTG TAG AG
GAG G CAAAGACAGTG CTTAAAAAGTGTAAAAGTG CCTTTTACATTCTAC CATCTATTAT CTCTAATG AG
AAG CAAG AAATT
CTTG G AA CTG TTTCTTG G AATTTG CG A G AAAT G CTTG CACATG CAG AAG AAACACG
CAAATTAATGC CTGTCTGTGTG GA
AACTAAAG CCATAGTTTCAACTATACAG CGTAAATATAAG G G TATTAAAATACAAG AG G GTGTGG TTG
ATTATG GTG CTA
G ATTTTACTTTTACACCAGTAAAACAACTG TAG
CGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAAT
G CCACTTG G CTATGTAACACATGG CTTAAATTTG G AAGAAG CTG CT C G G TAT ATG A G ATCT
CTC AAAG TG CCAG CTACAGT
TT CTG TTTCTTCACCTG AT G CTG TTAC AG CGTATAATG
GTTATCTTACTTCTTCTTCTAAAACACCTGAAG AACATTTTATTG
AAACCATCTCACTTG CT G GTTCCTATAAAG ATTG GTCCTATTCTG GACAATCTACACAACTAG GTATAG
AATTT CTTAAG AG
AG G TG ATAAAAG TG TATATTACACTAG TAATCCTACCACATTCCA CCTAG ATG G
TGAAGTTATCACCTTTG AC AATCTTAAG
ACACTTCTTTCTTTGAG AG AAGTG AG GACTATTAAG GTG TTTACAACAG TAG
ACAACATTAACCTCCACACG CAA GTTGTG
G AC ATG T CAATG ACATATG G ACAACAGTTTG GTCCAACTTATTTG GATG GAG CTG
ATGTTACTAAAATAAAACCTCATAAT
TC AC ATG AAG G TAAAA CATTTTAT G TTTTACCTAATG AT G ACACTCTA C G TG TTG AG G
CTTTT G AG TACTAC CACACAACTG
ATCCTAGTTTTCTG G GTAG GTACATGTCAG CATTAAATCACACTAAAAAGTG GAAATACCCACAAGTTAATG
GTTTAACTT
CTATTAAATG G G CAG ATAACAACTGTTATCTTG CCACTG CATTG TTAACA CTC CAACAAATAG AG
TTG AAGTTTAAT CCA CC
TG CT CTACAAG AT G CTTATTACAG AG CAAG G G CTG GTG AAG CTG CTAACTTTTGTG CA
CTTATCTTAG CCTACTGTAATAA
G AC AG TAG GTG AG TTAG GTGATGTTAG AG AAAC AAT G A G TTA CTTGTTTCAACATG
CCAATTTAG ATTCTTG CAAAAG AG
TCTTG AA CGTG GTGTGTAAAACTTGTG G ACAACAG C AG ACAA CCCTTAAG G G TG TA G AA G
CTGTTATGTACATG G G CAC A
CTTTCTTATG AACAATTTAAG AAA G GTGTTCAGATACCTTGTACGTGTG GTAAACAAG CTACA
AAATATCTAG TA CAACAG
G AG TCAC CTTTTG TTATG ATGTCAG CA CCACCTG CT CAG TATG AA CTTAAG CAT G
GTACATTTACTTGTG CTAG TG AG TACA
CTG GTAATTACCAGTGTG GTCACTATAAACATATAACTTCTAAAG AAACTTTG TATTG CATAG AC G GTG
CTTTACTTACAAA
G T CCTC A G AATAC AAAG GTCCTATTACG G AT G TTTTCTA CAA AG AAAA CAG TTACAC
AACAACCAT AAAAC CAG TTACTTA
TAAATTG GATG G TG TTGTTTG TACAG AAATT G AC CCTAAG TTG GACAATTATTATAAG AAAG
ACAATT CTTATTTC A CAG A
G C AACCAATTG AT CTT G TACC AAACCAACCATATCCAAAC G CAAG CTT C G ATAATTTTAAG TTT
G TAT G TG ATAATATCAAA
TTTG CT G ATG ATTTAAACCAGTTAACTG GTTATAAG AAACCTG CTTCAAG AG AG
CTTAAAGTTACATTTTTCCCTG ACTTAA
ATG GTG ATGTG GTG G CT ATTG ATTATAAACACTACACACCCTCTTTTAAG AAAG GAG
CTAAATTGTTACATAAACCTATTG
TTTGG CATGTTAACAATG CAACTAATAAAG CCACGTATAAACCAAATACCTG G TG TATAC G TT
GTCTTTG GAG CACAAAAC
CAGTTG AAACAT CAAATT C G TTTG ATG TA CTG AA G TCAG AG G AC G C G CAG G GAATG
GATAATCTTG CCTGC GAAGATCTA
AAACC AG TCTCTG AAG AAG TAG TG G AAAATC CTACCATACAG AAAG AC GTTCTTG A G TG
TAATG T G AAAACTACC G AAG T
TG TAG G AG ACATTATACTTAAACCAG CAAATAATAGTTTAAAAATTACAG AAG AG GTTG G CCACACAG
ATCTAATG G CTG
CTTATG TAG A CAATTCTAGTCTTACTATTAAG AAACCTAATG AATTATCTAG AG TATTAG GTTTG
AAAACCCTTG CTACTCA
TG GTTTAG CT G CTGTTAATAGTGTCCCTTG G G ATACTATAG CTAATTATG CTAAG
CCTTTTCTTAACAAAGTTGTTAGTACA
ACTACTAACATAG TTACACG GTGTTTAAACCGTGTTTGTACTAATTATATG CCTTATTTCTTTACTTTATTG
CTACAATTGTG
TACTTTTACTAG AAGTACAAATTCTAGAATTAAAG C ATCTATG CC G ACTACTATAG
CAAAGAATACTGTTAAG AG TG TC G G
TAAATTTTGTCTAG AG G CTTCATTTAATTATTTG AAGTCACCTAATTTTTCTAAACTG
ATAAATATTATAATTTG GTTTTTACT
ATTAAGTGTTTG CCTAG G TTCTTTAAT CTACTCAA CC G CTG CTTTAG GTGTTTTAATGTCTAATTTAG
G CATG CCTTCTTACT
GTACTG G TTA CAG AG AA G G CTATTTGAACTCTACTAATGTCACTATTG CAACCTACTGTACTG G TT
CTATA CCTT G TAG TG T
TTGTCTTAGTG GTTTAG ATT CTTTAG AC ACCTATCCTTCTTTAG AAA CTATA CAAATTAC CATTTCAT
CTTTTAAATG G GATTT
AACTGCTTTTG G CTTAGTTG CAGAGTG GTTTTTG G CATATATTCTTTTCACTAG GTTTTTCTATGTACTTG
GATTG G CTG CAA
TCATG CA ATTG TTTTTCAG CTATTTTG CAGTACATTTTATTAGTAATTCTTG G CTTATGTG
GTTAATAATTAATCTTGTACAA
ATG G CCCCGATTTCAG CTATG GTTAGAATGTACATCTTCTTTG CATCATTTTATTATGTATG G
AAAAGTTATGTG CATGTTG
TAG ACG G TTG TAATT C ATC AACTT G TAT G ATG TG TTACAAA C G TA ATA G AG CAAC
AAG AG T C G AATG TAC AACTATTG TTA
ATG GTGTTAG AAG GTCCTTTTATGTCTATG CTAATG G AG GTAAAG G CTTTTG CAAACTACACAATTG
GAATTGTGTTAATT
GTGATACATTCTGTG CTG G TAG TACATTTATTAGTG AT G AAGTTG C G AG A G ACTTG T
CACTACAG TTTAAAAG ACCAATAA
ATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTG AAGAATG G TTCCATC CAT CTTTACTTT G
ATAAAGCTG G
TCAAAAGACTTATGAAAG ACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTG AG A G
CTAATAACACTAAAG G TT CATT G
CCTATTAATGTTATAGTTTTTGATG GTAAATCAAAATGTGAAGAATCATCTGCAAAATCAG C G T CTG
TTTACTAC AG TC AG C
TTATG T G TCAA CCTATACTG TTACTAG AT CAG G CATTAGTGTCTG ATG TT G GTGATAGTG CG G
AAGTTG CAGTTAAAATGT
TT G ATG CTTA C G TTAATA C G TTITCAT CA A CTTTTAA C G TA CC AAT G G A AAAA CT
CAAAA C A CTA G TTG CAA CT G CA G AA G C
TG AACTTG CAAAG AAT G TG T CCTTAG AC AATGTCTTATCTACTTTTATTTCAG CAG CT C G G
CAAG G GTTTGTTGATTCAG AT
G TAG AAA CTAAA G ATG TTG TTG AATG T CTTA AATTG TCA CATCAATCT G AC ATA G AAG
TTA CTG G C G ATAG TT G TAATAAC
TATATG CTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTG GTG CTTGTATTG ACTGTAGTG CG
CGTCATATT
AATG CG C AG G T AG CAAAAAGTCACAACATTG CTTTGATATG G AA C G TTAAA G ATTTCAT G
TCATTG T CTG AACAACTAC G A

AAACAAATACGTAGTG CTG CTAAAAAG AATAA CTTACCTTTTAAG TT G ACAT GTG CAACTACTAG
ACAAG TT G TTAAT G TT
GTAACAACAAAGATAG CACTTAAGG GTG GTAAAATTGTTAATAATTG G TTG AA G
CAGTTAATTAAAGTTACACTTGTGTTC
CTTTTTGTTG CTG CTATTTTCTATTTAATAA CACCT G TT CATG TCATG TCTAAACATACTG A
CTTTTCAAG TG AAATCATAG G
ATACAAG G CTATTGATGGTG GTGTCACTCGTGACATAG CAT CTACAG AT ACTTG TTTTG
CTAACAAACATG CTGATTTTG A
CAC ATG GTTTAG CCAG CGTG GTG GTAGTTATACTAATGACAAAG CTTG CCCATTGATTG CTG CAG
TCATAACAAG AG AAG
TG G GTTTTGTCGTG CCTG GTTTG CCTG G CACGATATTACG CACAACTAATG GTG ACTTTTTG
CATTTCTTACCTAG AG TTTT
TAG TG C AGTT G G TAACAT CTG TTACA CACCATCAAAACTTATA G AG TACACTG ACTTTG
CAACATCAG CTTGTGTTTTG G CT
G CTG AAT GTACAATTTTTAAAG AT G CTTCTGGTAAG CCAG TACCATATT G TTATG ATACCAATG TA
CTAG AAG GTTCTGTTG
CTTATG AAAGTTTACG CCCT G ACA CAC G TTATG TG CTCATG G AT G G CT CTATTATT
CAATTTCCTAA CAC CTACCTTG AAGG
TT CTG TTAG A G TG GTAACAACTTTTG ATTCTG AG TA CT G TAG G CAC G G CACTTG T G
AAA G ATCA G AAG CTG GTGTTTGTGT
ATCTACTAGTG G TA G ATG G GTACTTAACAATGATTATTACAGATCTTTACCAG G AG TTTTCTG TG G
TG TAG AT G CTG TAAA
TTTACTTACTAATATG TTTA CAC CA CTAATTCAAC CTATTG GTG CTTTG G ACATATC AG
CATCTATAG TAG CTG G TG GTATT
G TAG CTATCGTAGTAACATG CCTTG CCTACTATTTTATG AG GTTTAG AAG AG CTTTTG GTG
AATACAGTCATGTAGTTG CCT
TTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTG
GTGTTTATTCTGTTAT
TTACTTG TACTTG AC ATTTTATCTTACT AATG AT G TTTCTTTTTTAG C AC ATATTCAG TG G ATGG
TTATG TT CACAC CTTTAG T
ACCTTTCTG GATAACAATTG CTTATATCATTTGTATTTCCACAAAG CATTTCTATTG G TTCTTTAG
TAATTACCTAAAG A G AC
G T G TAG TCTTTAATG GTGTTTCCTTTAGTACTTTTGAAGAAG CT G CG CTGTG CACCTTTTTG
TTAAATAAAG AAAT G TAT CT
AAAGTTG CG TA G TG ATG TG CTATTACCTCTTACG CAATATAATAG ATACTTAG CT CTTTATAATAAG
TA CAAGTATTTTAG T
G GAG CAATG GATACAACTAG CTACAG A G AAG CTG CTTG TT G TCATCTC G CAAAG G
CTCTCAAT G ACTT CAG TAACTC AG G
TT CTG ATG TTCTTTACCAACCACCACAAA CCT CTATCA CCTCA G CTGTTTTG CA G AG T G
GTTTTAGAAAAATG G CATTCCCA
TCTG GTAAAGTTG AG G GTTGTATG GTACAAGTAACTTGTG GTACAACTACACTTAACG GTCTTTG
GCTTGATG AC G TAG TT
TACTGTCCAAG AC ATG TGATCTG CACCTCTG AAG AC ATG CTTAACCCTAATTATGAAG
ATTTACTCATTCGTAAGTCTAATC
ATAATTTCTTG GTACAG G CTG G TAATG TT CAACT CA G G GTTATTG G ACATTCTATG
CAAAATTGTGTACTTAAG CTTAAG G
TT G ATAC AG CC AATCCTAAG A CACCTAAG TATAAG TTTG TTC G CATTCAACCAG G AC AG
ACTTTTTCA G TG TTAG CTTGTTA
CAATGGTTCACCATCTG GTGTTTACCAATGTG CTAT G AG G CCCAATTTCACTATTAAGG G TT CATTC
CTTAATG GTTCATGT
G G TAG T G TTG GTTTTAACATAG ATTATGACTGTGTCTCTTTTTGTTACATG CACCATATG
GAATTACCAACTG G AG TTC ATG
CTG G CAC AG ACTTAG AA G GTAACTTTTATG G ACCTTTTGTTG ACAG G CAAAC AG C AC AAG
CAG CTG GTACG GACACAACT
ATTACAGTTAATGTTTTAGCTTG GTTGTACG CTGCTGTTATAAATG G AG ACAG GTG GTTTCTCAATCG
ATTTACCACAACTC
TTAATG ACTTTAACCTTGTG G CTATG AAGTACAATTATG AACCTCTAACACAAG ACCAT G TT G
ACATACTA G G AC CT CTTTC
TG CT CAA ACTG G AATT G CC GTTTTAG ATATGTGTG CTTCATTAAAAGAATTACTG CAAAATG
GTATGAATGG ACGTACCAT
AUG GGTAGTG CTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATG CTCAG
GTGTTACTTTCCAAAGTG CA
GTGAAAAG AACAATCAAG G GTACACACCACTG G TTG TTACT CACAATTTTG A CTTCA CTTTTAG
TTTTAGT CCAG A G TACTC
AATG GT CTTT G TTCTTTTTTTTG TATG AAAATG CCTTTTTACCTTTTG CTATG G GTATTATTG
CTATGTCTGCTTTTG CAAT G A
TGTTTGTCAAACATAAG CAT G CATTTCTCTGTTTG TTTTTG TTACCTT CT CTT G CC ACTG TA G
CTTATTTTAATATG GTCTATA
TG CCTG CTAGTTG G GTGATG C G TATTATG AC ATG GTTG GATATG GTT G ATAC TAG TTTG T
CTG GTTTTAAGCTAAAAG ACT
GTGTTATGTATG CAT CAG CTGTAGTGTTACTAATCCTTATG ACAG CAAGAACTGTGTATG ATGATG GTG
CTAG G AG AGTG
TG GACACTTATGAATG TCTTGACACTCGTTTATAAAGTTTATTATG GTAATG CTTTAG ATCAAG
CCATTTCCATGTG G G CTC
TTATAATCTCTG TTACTTCTAACTACTC AG G TG TAG TTACAACT G T CATG TTTTTG G CCAG AG
GTATTGTTTTTATG TG TG TT
G AG TATT G CC CTATTTTCTTCATAACTG GTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAG G
CTATTTTTG TACT
TGTTACTTTG G CCTCTTTTGTTTACTCAACCG CT ACTTTAG A CTG A CTCTTG GTGTTTATG
ATTACTTAGTTTCTACACAG G A
GTTTAG ATATATG AATTCAC AG GG ACTA CTCCC ACCCAAG AATAG CATAG AT G
CCTTCAAACTCAACATTAAATTGTTG GG
TGTTG GTGG CAAAC CTTG TATC AAA GTAG CC A CT G TA CAG T CTAAAATG T CAG ATG
TAAAG TG C ACAT CAG TA G TCTTACT
CTC A G TTTTG CAACAACTCAG AG TA G AATC ATCAT CTAAATTGT G G G
CTCAATGTGTCCAGTTACACAATGACATTCTCTTA
G CTAAAGATACTACTG AAG CCTTTGAAAAAATG GTTTCACTACTTTCTGTTTTG CTTTCCATG CAG G GTG
CTGTAGACATAA
ACAAGCTTTGTGAAG AAATG CTG GACAAC AG G G CAA CCTTAC AAG CTATAG CCTC A G AG
TTTAG TTC CCTT CCATC ATATG
CAG CTTTTG CTACTG CTCAAGAAG CTTATG AG CAGG CTGTTG CTAATG GTG ATTCTG AAG TTG
TTCTTAAAAA GTTG AAG A
AGTCTTTGAATGTG G CTAAATCTG AATTTG AC CGTG ATG CAG CCATG CAACGTAAGTTG GAAAAGATG
G CTGATCAAG CT
ATG ACCC AAATG TATAAAC AG G CTAG AT CTG AG G ACAA G AG G G CAAAAGTTACTAGTG
CTATG CAG ACAATG CTTTTCAC
TATG CTTAGAAAGTTG GATAATGATG CACT CAAC AACATTATCAAC AATG CAAG AG ATG
GTTGTGTTCCCTTGAACATAAT
ACCTCTTACAACAG CAG CCAAACTAATG G TTG TCATA CCAG A CTATAACAC ATATAAAAATAC G TG
TG ATG G TAC AA CATT
TA CTTATG CAT CAG CATTGTG G G AA ATCCAA CAG GTTGTAG ATG
CAGATAGTAAAATTGTTCAACTTAGTGAAATTAGTAT
G GACAATTCACCTAATTTAG CATG G CCTCTTATTGTAACAG CTTTAAG GG CCAATTCTG CTG
TCAAATTACA G AATAATG A
G CTTAGTCCTGTTG CACTACGACAGATGTCTTGTG CTG CCG GTACTACACAAACTGCTTG CA CTG ATG
AC AATG CGTTAG C
TTACTACAACACAACAAAG G GAG GTAG GTTTGTACTTG CACTGTTATCCG ATTTACAG GATTTGAAATG G
G CTAGATTCCC
TAA G AG T G ATG GAACTG GTACTATCTATACAGAACTG GAACCACCTTGTAG GTTTGTTACAG AC
ACAC CTAAA G GTCCTAA

AG T G AAG TATTTATACTTTATTAAAG GATTAAACAACCTAAATAG AG G TATG G TACTTG G TAG
TTTAG CTG CCACAGTACG
TCTACAAG CTG GTAATG CAACAGAAGTG CCTG CCAATTCAACTG TATTATC TTT CT G TG CTTTTG
CT G TAG ATG CT G CT AAA
G CTTACAAAGATTATCTAG CTAGTG GG G G ACAACCAAT CACTAATTG TG TTAAG AT GTTGTG
TACACA CACTG GTACTG GT
CAG G CAATAACAGTTACACCG G AAG CCAATATG GATCAAGAATCCTTTG GTG GTG CATC
GTGTTGTCTGTACTG CC GTTG C
CAC ATAG ATCAT C CAAAT CCTAAAG GATTTTGTG ACTTAAAAG
GTAAGTATGTACAAATACCTACAACTTGTG CTAAT G AC
CCTGTG G GTTTTACACTTAAAAACACAGTCTGTACC GTCTG CG G TAT G TG GAAAG GTTATG G CTG
TAG TTG TG ATCAACTC
CG CGAACCCATG CTTCAGTCAG CTG ATG CACAATCGTTTTTAAACG GGTTTG CG
GTGTAAGTGCAGCCCGTCTTACACCGT
G CG G CA CAG G CACTAG TACT GATGTC GTATAC AG G G CTTTTGACATCTACAATGATAAAG TAG
CTG GTTTTG CTAAATTCC
TAAAAACTAATTG TTGTCG CTTCCAAG AAAAGG ACG AAG ATGACAATTTAATTG ATTCTT ACTTTG
TAGTTAAG AG ACACA
CTTTCTCTAACTACCAACATG AAG AAACAATTTATAATTTACTTAAG GATTGTCCAG
CTGTTGCTAAACATGACTTCTTTAA
GTTTAG AATAGACG G TG AC ATG G TACCACATATATCACGTCAACGTCTTACTAAATACACAATG G CAG
A CCTC G TCTATG C
TTTAAG G CATTTTG ATGAAG
GTAATTGTGACACATTAAAAGAAATACTTGTCACATACAATTGTTGTGATGATGATTATTTC
AATAAAAAG GACTG GTATG ATTTTG TAG AAAA CCCAG ATATATTAC G CG TATA CG CCAACTTAG
GTG AACGTGTACG CCA
AG CTTT G TTAAAAACA G TA C AATTCTG T G ATG CCATG CGAAATG CTG GTATTGTTG G TG
TACT G ACATTAG ATAAT CAAG A
TCTCAATG GTAACTG G TAT G ATTTCG GTGATTTCATACAAACCACG CCAG G TAG T G G AG
TTCCTG TT GTAG ATTCTTATTAT
TCATTGTTAATG CCT ATATTAACCTTG AC CAG G GCTTTAACTG CAG AG TC ACATG TTG A CACTG
ACTTAACAAA G CCTTACA
TTAAGTG G G ATTTG TTAAAATAT G A CTTCACG GAAG AG AG G TTAAAA CT CTTT G ACC G
TTATTTTAAATATTG G G AT CAG A
CATACCACCCAAATTGTGTTAACTGTTTG G ATG ACAGATG CATTCTG CATTGTG CAAACTTTAATG
TTTTATTCT CTAC AG T
GTTCCCACCTACAAGTTTTG G ACCACTAG TG AG AAAAATATTTGTTGATG GTG TTCCATTTG TAG
TTTCAACTG GATACCAC
TTCAG AG AG CTAG GTGTTGTACATAATCAG G ATGTAAACTTACATAG CT CTAG ACTTAGTTTTAAG G
AATTACTTGTG TAT
G CTG CT G ACC CTG CTATG CACG CTG CTTCTG GTAATCTATTACTAGATAAACG CACTACGTG
CTTTT CAG TAG CT G CACTTA
CTAACAATGTTG CTTTTCAAACTGTCAAACCCG GTAATTTTAACAAAG ACTTCTATG ACTTTGCTGTGTCTAAG
G G TTTCTTT
AAG GAAG GAAGTTCTGTTG AATTAAAACACTTCTTCTTTG CT CAG G ATG GTAATG CTG CTATC AG
CG ATTATGACTACTAT
CGTTATAATCTACCAACAATGTGTGATATCAG
ACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACG
ATG GTG G CTGTATTAATG CTAACCAAG T CATCG TCAACAACCTAG AC AAATC AG CTG
GTTTTCCATTTAATAAATG G G G TA
AG G CTAG A CTTTATTATG ATTC AATG A G TTATG AG G AT CAAG ATG C A CTTTTCG C
ATATACAAAAC G TA ATG T CATCCCTAC
TATAACTCAAATG AATCTTAAGTATG CCATTAGTG C AAA G AATAG AG CTCG C ACCG TAG CTG GTG
TCT CTAT CTG TAG TAC
TATG ACC AATAG ACAGTTTCATCAAAAATTATTGAAATCAATAG CCGCCACTAG AG GAG
CTACTGTAGTAATTG GAACAA
G CAAATTCTATG GTG GTTG G CACAACATGTTAAAAACTGTTTATAGTG ATG TAG AAAACCCT
CACCTTATG G GTTG G GATT
ATCCTAAATGTG ATAG AG CCATGCCTAACATG CTTAGAATTATGG CCTCACTTGTTCTTG CTCG C AAA
CATAC AACG TG TTG
TAG CTTG TCACACCGTTTCTATAG ATTAG CTAATG AG TG TG CTCAAG TATTG AG TG AAATG
GTCATGTGTGG CG GTTC ACT
ATATGTTAAACCAG GTGGAACCTCATCAG G AG ATG CCACAACTG CTTATG
CTAATAGTGTTTTTAACATTTGTCAAGCTGT
CAC G GCCAATGTTAATG CACTTTTATCTACTGATG GTAACAAAATTG CC G ATAAGTATGTCCG
CAATTTACAACACAG ACTT
TAT G AG TGTCTCTATAG AAATAG A G ATG TTG ACACAG ACTTTGTGAATG AGTTTTACG CATATTTG
CGTAAACATTTCTCAA
TG ATGATACTCTCTG ACG AT G CT G TTG TG T G TTTCAATAG CACTTAT G CAT CTCAAG GT
CTAG T G G CTAG CATAAAG AACT
TTAA G TC AG TT CTTTATTAT CAAAAC AATG TTTTTAT G TCTG AAG CAAAATGTTG GACTG AG
ACTG AC CTTAC TAAAG G ACC
TCATG AATTTTG CTCTCAACATACAATG CTAGTTAAACAGG GTG ATG ATTAT G TG TACCTTC
CTTACCC AG AT CCATC AAG A
ATCCTAG GG G CCG G CTGTTTTG TAG ATG ATATCG TAAAAACAGATG GTACACTTATGATTG AACG
GTTCG TGTCTTTAG CT
ATAGATG CTTA CC CACTTACT AAACAT CCTAATCAG GAG TATG
CTGATGTCTTTCATTTGTACTTACAATACATAAG AAAG C
TAC ATG ATG AG TTAA CAG G ACACATGTTAGACATGTATTCTGTTATGCTTACTAATG ATAACACTTCAAG
GTATTG G GAAC
CTG AGTTTTATG AG G CTATG TACACAC CG CATACAG TCTTAC AG G CTGTTG G G G CTTG TG
TT CTTTG CAATTCACAG ACTTC
ATTAAG AT G TG GTG CTTG CATACG TAG ACCATTCTTATGTTGTAAATG CTG TTACG A CCATG
TCATATCAAC ATCAC ATAAA
TTAGTCTTGTCTGTTAATCCGTATGTTTG CAATG CTCCAG G TT G TG ATGTCACAG ATG T G ACT
CAACTTTACTTAG GAG G TA
TG AG CTATTATTGTAAATCACATAAACCAC CCATTAGTTTTCCATTGTGTGCTAATG GACAAGTTTTTG
GTTTATATAAAAA
TACATGTGTTG G TAG CGATAATGTTACTGACTTTAATG CAATTG CAA CATG TG A CT G G AC AAATG
CTG GTGATTACATTTT
AG CTAAC ACCTG TACT G AAA G ACT CAAG CTTTTTG C AG CA G AAACG CTCAAAG CT ACTG
AG G AG A C ATTTAAACT G TCTTA
TG GTATTG CTACTGTACGTG AA GT G CTG TCTG ACAG AG AATTACATCTTTCATG G G AAG TT G
GTAAACCTAGACCACCACT
TAACCGAAATTATGTCTTTACTG GTTATCGTGTAACTAAAAACAGTAAAGTACAAATAGG AG AG TACACCTTTG
A AAAAG G
TG ACTATG GTGATG CTGTTGTTTAC CG AG GTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTG
CTGACATCACAT
ACAGTAATG CCATTAAGTG CA CCTA C ACTAG TG C CACAAG AG CA CTATG TTAG AATTACTG G
CTTATACCCAACACTCAAT
ATCTCAG ATG AGITTTCTAG CAATGTTG CAAATTATCAAAAG GTTG GTATG CAA AAGTATTCTA CA
CTCCAG G G A CCA CCT
G G TACT G G TAAG AG TCATTTTG CTATTG G CCTAG CTCTCTACTACCCTTCTG CT CG
CATAGTGTATACAG CTTG CTCTCATG
CCG CTGTTGATG CACTATGTG A G AAG GCATTAAAATATTTG CCTATAG ATAAATG TAG TAG
AATTATACCTG CA C G TG CTC
G T G TAG AG TG TTTTG ATAAATT CAAAG T G AATTCAA CATTAG AACA G TAT G TCTTTT G
TACTG TAAATG CATTG CCTG AGA
CG ACAG C AG ATATAG TTG T CTTT G ATG AAATTTCAATGG C CACAAATTAT G ATTTG A G TG
TTG TC AATG CCAG ATTACGTG

CTAAGCACTATGTGTACATTG G CG ACCCTG CTCAATTACCTG CACCACG CACATTG CTAACTAAG G G
CACACTAG AACCAG
AATATTTC AATTC AG TG TGTAG ACTTATG AAAACTATAG GTCCAG ACATGTTCCTCG G AACTTGTCG
G CGTTGTCCTG CTG
AAATTG TT G ACA CTG T G AG TG CTTTG GTTTATGATAATAAG CTTAAAG CAC ATAAAG
ACAAATCAG CT CAAT G CTTTAAAA
TGTTTTATAAG G G TG TTAT CAC G C ATG AT G TTT CAT CTG C AATTAA C AG G
CCACAAATAG G CG T G G TAAG AG AATTC CTTA
CAC GTAACCCTG CTTG G AG AAAAG CTG TCTTTATTTCAC CTTATAATTCACAG AATG CTG TAG
CCTCAAAG ATTTTG G GA CT
ACC AACT C AAACTG TTG ATTC ATC AC AG G G CTCAG AATAT G ACTATGT CATATTCACTC AAA
CCACTG AAAC AG CTC ACTCT
TGTAATG TAAAC AG ATTTAAT G TT G CTATTAC CAG AG CAAAAG TAG G CATACTTTGCATAATG
TCTG ATAG A G ACCTTTAT
G AC AAG TTG CAATTTACAAG TCTT G AAATTCCAC G TAG GAATGTG G CAACTTTACAAG
CTGAAAATGTAACAG G ACT CTTT
AAAG ATTG TAG TAAG GTAATCACTG G GTTACATCCTACACAG G CAC CTACA C ACCT CAG TG TTG
ACACTAAATTCAAAACT
GAAG GTTTATGTGTTGACATACCTG GCATACCTAAG G ACATGACCTATAG AAG ACT CATCTCTATG ATG
G GTTTTAAAATG
AATTATCAAGTTAATG GTTACCCTAACATGTTTATCACCCG CGAAGAAG CTATAAGACATGTACGTG CATG
GATTG G CTTC
G ATGTC G AG G G GTGTCATG CTACTAG AG AAG CT GTTG GTACCAATTTACCTTTAC AG CTAG
GTTTTTCTACAG GTGTTAAC
CTAGTTG CTG TACCTACAG G TTAT G TT G ATAC ACCTAATAATACAG ATTTTT CCAG A G TTA G
TG CTAAACCACCG CCTG GA
G AT CAATTTAAA CACCT CATACCACTTATG TACAAAGG ACTTCCTTG G AATGTAGTG
CGTATAAAGATTGTACAAATGTTA
AGTG ACA CACTTAAAAAT CTCT CTG ACAG AG TCG TATTTGTCTTATG G G CA CATG
GCTTTGAGTTGACATCTATGAAGTATT
TTGTG AAAATAG G AC CTG AG CG CACCTGTTGTCTATGTG ATAG ACGTGCCACATG CTTTTCCACTG
CTTCAGACACTTATG
CCTGTTG G CATCATTCTATTG GATTTGATTACGTCTATAATCCGTTTATGATTG ATGTTCAACAATG G
GGTTTTACAGGTAA
CCTACAAAG CAACCATGATCTGTATTGTCAAGTCCATG G TAATG CAC ATG T AG CTAG TTG TG AT G
C AAT CATG A CTAG GTG
TCTAG CTG TC CAC G AG TG CTTTGTTAAG CGTGTTG ACTG GACTATTG AATATCCTATAATTG G T
G AT G AACT G AAG ATTAA
TG CG G CTTG TAG AAAG GTTCAACACATG GTTGTTAAAG CT G CATTATTAG CA G ACAAATTCCCA
G TTCTTCA C G A CATTG G
TAACCCTAAAG CTATTAAG TG TG TA CCTC AAG CT G ATG TAG AATG G AAG TT CTAT G ATG
CACAG CCTT G TAG TG ACAAAG C
TTATAAAATAGAAGAATTATTCTATTCTTATG CCACACATTCTGACAAATTCACAGATG GTGTATG CCTATTTTG
GAATTGC
AATGTCG ATAGATATCCTG CTAATTCC ATTG TTTG TAG ATTTG ACACTAG AGTG
CTATCTAACCTTAACTTG CCTG GTTGTG
ATG GTG G CAGTTTGTATGTAAATAAACATG CATT CC ACACAC CAG CTTTTG ATAAAAGTG
CTTTTGTTAATTTAAAACAATT
ACC ATTTTT CTATTACT CTG ACAGTCCATGTG AG T CT CATG G AAAA C AAG TAG TG TCAG
ATATAGATTATGTACCACTAAAG
TCTG CTACGTGTATAACACGTTG CAATTTAG GTG GTG CTG TCTG TAG A CATCAT G CTAATG AG
TACAG ATTG TATCT C G AT
G CTTATAACATGATG ATCTCAG CTG G CTTT AG CTTGTG G G TTTA CAAA CAATTT G ATA
CTTATAACCT CT G GAACACTTTTA
CAAG ACTT CAG A G TTT AG AAAATG T G GCTTTTAATGTTGTAAATAAG G G ACACTTTGATG G A
CAACAG G GT G AA G TACCA
G TTTCTATC ATTAATAAC ACTG TTTACACAAAAG TT G ATG G TG TTG AT G TAG AATTG TTTG
AAAATAAAAC AA C ATTACCTG
TTAATG TAG CATTTG AG CTTTG G G CTAAGCG CAACATTAAACCAGTACCAG AG
GTGAAAATACTCAATAATTTG GGTGTG
G AC ATTG CTG CTAATACTGTGATCTG G G ACTAC AAAAG A G ATG CTCCAG
CACATATATCTACTATTG GTGTTTGTTCTATG
ACT G ACATAG CCAAGAAACCAACTGAAACGATTTGTG CACCACTCACTGTCTTTTTTG ATG G TAG A G
TTG AT G G TCAAG TA
GACTTATTTAG AAATG CCCGTAATG GTG TTCTTATTACAGAAG GTAGTGTTAAAG GTTTACAACCATCTG
TAG GTCCCAAA
CAAG CTAGTCTTAATG GAGTCACATTAATTG GAG AAG CC GTAAAAACACAG TTCAATTATTATAAG AAAG
TTGATG GTG TT
GTCCAACAATTAC CTG AAA CTTACTTTACTC AG AG TAG AAATTTA CAAG AATTTAAACC CAG G AG
TCAAATG G AAATTG AT
TT CTTAG AATTAG CTATG GATGAATTCATTGAACG GTATAAATTAG AAG G CTATG
CCTTCGAACATATCGTTTATG G AG AT
TTTAGTCATAGTCAGTTAG GTG GTTTACATCTACTGATTGGACTAG CTAAACGTTTTAAG GAATCACCTTTTG
AATTAGAAG
ATTTTATTCCTATG G ACAG TA CAG TTAAAAACTATTTCATAACAG ATG CG CAAAC AG
GTTCATCTAAGTGTGTGTGTTCTGT
TATTG ATTTATTACTTG AT G ATTTTG TTG AAATAATAAAAT CCCAA G ATTTATCTG TA G TTTCTAA
G G TT GTC AAAG T G ACT
ATTG ACTATACAG AAATTTCATTTATG CTTTG GTGTAAAGATGG C CATG TAG AA ACATTTTAC
CCAAAATTACAATCTA G TC
AAG CGTG G CAACCG G GTGTTG CTATG CCTAATCTTTA CAA AATG CAAAGAATG
CTATTAGAAAAGTGTGACCTTCAAAATT
ATG GTG ATAGTG CAACATTACCTAAAG G CATAATGATGAATGTCG
CAAAATATACTCAACTGTGTCAATATTTAAACACAT
TAACATTAG CTG TACC CTATAATAT G AG AG TTATAC ATTTT G GTG CTG G TTCTG AT AAAG G
AG TT G CAC CAG G TA CAG CTG
TTTTAAGACAGTG GTTG CCTACG G GTACG CT G CTTGTCGATTCAG ATCTTAATG ACTTTGTCTCTG
ATG CAGATTCAACTTT
GATTG GTG ATTGTGCAACTG TACATAC AG CT AATAAATG G G
ATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAA
TGTTACAAAAGAAAATG ACTCT AAAG AG G GTTTTTTCACTTACATTTGTG G GTTTATACAACAAAAG
CTAG CT CTTG G AG G
TTCCGTG G CTATAAAG ATA ACAG AA CATTCTTG GAATG CTG ATCTTTATAAG CT CATG GG AC
ACTTCGCATG GTG GACAG C
CTTTGTTACTAATGTGAATG CGTCATCATCTG AAG CATTTTTAATTG GATGTAATTATCTTG GCAAACCACG
CGAACAAATA
G AT G GTTATGTCATG CAT G CAAATTACATATTTTG G AG G AATACAAATCCAATT C AG TT G
TCTTC CTATTCTTTATTTG AC AT
G AG TAAATTTC CC CTTAAATTAAG G GGTACTG CTGTTATGTCTTTAAAAGAAG GTCAAATCAATGATATG
ATTTTATCTCTT
CTTAGTAAAG GTAG ACTTATAA TTAG AG AAAACAACAG AGTTGTTATTICTAGTG ATG TICTIG TTAA
CAA CTAAAC G AA C
AATGTTTGTTTTTCTTGTTTTATTG CCA CTAGT CTCTAG TC AG TG TG TTAAT CTTAC AACCAG AACT
CAATTACCCCCTG CAT
ACACTAATTCTTTCACACGTG GTG TTTATTAC CCTG A CAAA G TTTT CAG ATCCTC AG TTTTAC
ATTC AACTCA G GACTTGTTC
TTACCTTTCTTTTCCAATGTTACTTGGTTCCATG CTATACATGTCTCTGG G ACCAATG GT ACTAAG AG
GTTTGATAACCCTGT
CCTACCATTTAATGATG GTGTTTATTTTG CTTCCACTG AG AAG TCTAACATAATAAG AG G CTG G
ATTTTTG GTACTACTTTA

G ATTCG AAG ACC CAGTC CCTACTTATTGTTAATAAC G
CTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATG
ATCCATTTTTG G GTGTTTATTACCACAAAAACAACAAAAGTTG GATG GAAAGTG
AGTTCAGAGTTTATTCTAGTG CG AATA
AUG CACTTTTGAATATGTCTCTCAG CCTTTTCTTATG GACCTTGAAG G AAAACAG G
GTAATTTCAAAAATCTTAG G GAATT
TGTGTTTAAG AATATTGATG GTTATTTTAAAATATATTCTAAG CACACG C CTATTAATTTAGTG CGT G AT
CTCCCTCAG G GT
TTTTCG GCTTTAG AACCATTG G TAG ATTTG CCAATAGGTATTAACATCACTAG GTTTCAAACTTTACTTG
CTTTA CATA G AA
GTTATTTGACTCCTG GT G ATT CTTCTTCA G G TTG G A CAG CT G GT G CT G CAG
CTTATTATGTG G GTTATCTTCAACCTAG G AC
TTTTCTATTAAAATATAATGAAAATG G AAC CATTAC AG ATG CTG TAG A CTG TG CACTTG AC
CCTCT CTCAG AAACAAAGTG
TACGTTG AAATC CTTCACTG TAG AAAAAG G AATCTATCAAACTTCTAACTTTAG AG TC CAACCAACAG
AAT CTATTG TTA G A
TTTCCTAATATTACAAACTTGTG CCCTTTTG GTGAAGTTTTTAACG C CA CCA G ATTTG CATCTGTTTATG
CTTG G AACAG GA
AGAGAATCAG CAACTGTGTTG CTGATTATTCTGTCCTATATAATTCCG CATCATTTTCCACTTTTAAGTGTTATG
G AGTGT CT
CCTACTAAATTAAATGATCTCTG CTTTACTAATGTCTATG C AG ATTCATTTG TAATTAG AG GTG ATG
AAGTCAG ACAAATCG
CTCCAG G GCAAACTG G AAAG ATT G CT G ATTATAATTATAAATTACCAG ATGATTTTACAG G CTG
CGTTATAG CTTG G AATT
CTAACAATCTTG ATTCTAAG GTTG GTG GTAATTATAATTACCTGTATAGATTG TTTAG G AAG
TCTAATCTCAAA CCTTTTG A
GAG AG ATATTTCAACTGAAAT CTATC AG GCCG GTAG CA CACCTTG TAATG GTG TT G AAG
GTTTTAATTGTTACTTTCCTTTA
CAATCATATG GTTTCCAACCCACTAATG GTGTTG G TTA CCAACC ATACA G AG TA G TA G TACTTTC
TTTT G AACTTCTACATG
CAC CAG CAACTGTTTGTG G ACCTAAAAAGTCTACTAATTTG
GTTAAAAACAAATGTGTCAATTTCAACTTCAATG GTTTAAC
AG G CA CA G G TG TTCTTACTG AG TCTAAC AAAAAG TTT CTG CCTTTCCAACAATTTG G CAG A
G ACATTG CTG A C ACTACTG A
TG CTGTCCGTGATCCACAG AC ACTTG AG ATTCTTG AC ATTA CACCATG TT CTTTTG GTG
GTGTCAGTGTTATAACACCAG GA
ACAAATACTTCTAACCAG G TT G CTGTTCTTTATCAG GATGTTAACTG C AC AG AAG TC CCTG TTG
CTATTCATG CAGATCAAC
TTACTCCTACTTG G CGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTG CAG G CTGTTTAATAG G G
G CTG AACATGT
CAA CAACT CATATG AG TGTG ACATACCCATTG GTGCAG GTATATG CG CTAG TTAT CAG ACT CAG
ACTAATT CTCCTC G G CG
G G CACG TAGTG TAG CTAGTCAATCCATCATTG CCTACACTATGTCACTTG GTG CAG AAAATTC AG
TTG CTTACT CTAATAAC
TCTATTG CCATACCC A CAAATTTTAC TATTAG TG TTAC CACAG AAATT CTAC CAG T G TCTATG A
CCAAG A CATC AG TAG AU
GTACAATGTACATTTGTG G TGATTCAACTGAATG C AG CAATCTTTTGTTG CAATATG G
CAGTTTTTGTACACAATTAAACCG
TG CTTTAACTG GAATAG CTG TTG AA CAAG AC AAAAACA CCCAAG AAGTTTTTG CA CAA G TCAAA
CAAATTTACAAAACACC
ACC AATTAAAG ATTTTG GTG GTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAG CAAG A G G
TCATTTATT G AA
G AT CTACTTTTC AAC AAAG TG AC ACTTG CAG AT G CTG GCTTCATCAAACAATATG GTG ATTG
CCTTG GTG ATATTG CTG CTA
GAG AC CT CATTT G TG CACAAAAGTTTAACG G CCTTACTGTTTTG CCACCTTTG CTCACAGATG
AAATG AUG CTCAATACAC
TT CTG CACTGTTAG CG G GTACAATCACTTCTG GTTG G ACCTTTG GTG CAGGTGCTG
CATTACAAATACCATTTG CTATG CA
AATG GCTTATAG GTTTAATG GTATTG G AG TTACA CAG AATGTTCTCTATG AG AACCAAAAATTG
ATTG CCAACCAATTTAA
TAG TG CT ATTG G CAAAATTCAAGACTCACTTTCTTCCACAG CAAGTG CACTTG GAAAACTTCAAGATGTG
GTCAACCAAAA
TG CACAAG CTTTAAACACG CTTGTTAAACAACTTAG CT C CAATTTTG GTG
CAATTTCAAGTGTTTTAAATG ATATC CTTT CAC
GTCTTG ACAAAGTTG AG G CTGAAGTG CAAATTGATAG G TT G ATCACAG G CAGACTTCAAAGTTTG
CA G ACATATGTG ACT
CAAC AATTAATTA G AG CTG CAG AAATC AG AG CTTCTG CTAATCTTG CTG CT ACTAAAATG T
CAG AG TGTGTACTTG GACAA
TC AAAAAG AG TTG ATTTTTGTG GAAAG G G CTATCATCTTATGTCCTTCCCTCAGTCAG CACCTCATGG
TGTAGTCTTCTTG C
ATG TG A CTTAT G TC CCTG CACAAG AAAAG AACTTCACAACTG CTCCTG CCATTTGTCATGATG
GAAAAG CAC A CTTT CCT C
GTG AAG GTGTCTTTGTTTCAAATG G CACAC A CTG GTTTGTAACACAAAG G AATTTTTATG AAC CA C
AAATCATTACT ACAG
ACAACACATTTGTGTCTG G TAACTG TG AT G TT G TAATAG G
AATTGTCAACAACACAGTTTATGATCCTTTG CAACCTGAATT
AG A CTCATTCAAG GAG G AG TTAG ATAAATATTTTAAGAATCATACATCACCAG ATGTTGATTTAG GTG
ACATCTCTG G CAT
TAATG CTT CAG TTG TAAACATTCAAAAAG AAATTG A CCG C CTCAAT G AG GTTG CCAAG
AATTTAAATG AATCT CTCAT C G A
TCTCCAAG AACTTG G AAAG TATG AG CAGTATATAAAATG G CCATGGTACATTTGG CTAG GTTTTATAG
CTG G CTTGATTG C
CATAGTAATG G TG AC AATTATG CTTTG CTGTATG ACCAGTTG CTG TAG TT G TCTCAAG GG CTG
TT G TT CTTG TG G ATCCTG C
TG CAAATTTG ATG AAG AC G ACT CTG AG CCAG TG CT CAAAG G AG TC AAATTA CATTAC
ACATAAAC G AACTTATG GATTTGT
TTATG AG AATCTTCACAATTG G AA CTG TAACTTTG AAG CAAG GTG AAATCAAG GATG
CTACTCCTTCAGATTTTGTTCG CG
CTACTG CAACGATACCGATACAAG CCTCACTCCCTTTCG GATG G CTTATTGTTG G CGTTG CACTTCTTG
CTGTTTTTCAG AG
CG CTTC CAAAATCATAACCCTCAAAAAG AG ATG G CAA CTAG CA CTCTC CAAG G
GTGTTCACTTTGTTTG CAACTTG CTG TT
G TTG TTTG TAACAG TTTA CTCAC A CCTTTTG CTCGTTG CTG CTG GCCTTG AAG
CCCCTTTTCTCTATCTTTATG CTTTAGTCTA
CTT CTT G CAG A G TATAAACTTTG TAAG AATAATAAT G AG G CTTTG G CTTTG CTG GAAATG
CC G TTC CAAAAA C CCATTACTT
TATG ATG CCAACTATTTTCTTTG CTG G CATACTAATTG TTAC G ACTATTG TATACCTTAC
AATAGTGTAACTTCTT CAATT GT
CATTACTTCAG GTG ATG G C ACAA CAAG T CCTATTTC TG AA CATG ACTA C CAG ATTG G
TGGTTATACTG AAAAATG G G AATC
TG G A G TAAAA G ACT G TG TTG TATTA C A CA G TTA CTTCACTTCA G A CTATTA CCA G
CTG TA CTCAA CTCA ATTG A G TA CA G AC
ACTG GTGTTG AACATG TTACCTTCTT CATCTACAATAAAATTG TTG ATG AG CCTG
AAGAACATGTCCAAATTCACACAATCG
ACG GTTCATCCG G AG TTG TTAATCCAG TAATG G AACC AATTTATG ATG AAC CG AC G AC G
ACTACTAG CGTG CCTTTGTAAG
CAC AAG CTGATG AG TA C G AACTTATG TACT CATT C G TTT C G G AAG A G AC AG
GTACGTTAATAGTTAATAG CGTACTTCTTT
TT CTTG CTTTCGTG GTATTCTTG CTAGTTACACTAG CCATCCTTACTG CG CTTC GATTGTGTG
CGTACTG CTG CAATATTG TT

AACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTC
TG GT
CTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTA
CCGT
TGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAA
TTT
GCCTATG CCAACAGGAATAG GTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAG
CTTGTT
TTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTG GAATTGCTATCG
CAATGGCTTGTCTTGTAGGCTTGATGT
GGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACAT
TCT
TCTCAACGTGCCACTCCATGGCACTATTCTGACCAGACCGCTTCTAGAAAGTGAACTCGTAATCGG AG CTGTG
ATCCTTCG
TG GACATCTTCGTATTG CTG G ACACCATCTAG GACG CTGTGACATCAAG GACCTG
CCTAAAGAAATCACTGTTGCTACATC
ACG AACG CTTTCTTATTACAAATTG G GAG CTTCG CAG CGTGTAG
CAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAG
GATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACA
GA
TGTTTCATCTCGTTGACTTTCAG GTTACTATAGCAGAG ATATTACTAATTATTATG AG
GACTTTTAAAGTTTCCATTTGGAAT
CTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAG
AGC
AACCAATG GAG
ATTGATTAAACGAACATGAAAATTATTCTTTTCTTGGCACTGATAACACTCGCTACTTGTGAGCTTTATCA
CTACCAAGAGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCA
TT
TCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAA
CAC
GTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAGACAAGAG
GAAGTTCAAGAACTTTACTCTCCAATTT
TTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTG
AACTTTCATTAATT
GACTTCTATTTGTG CTTTTTAG CCTTTCTG CTATTCCTTGTTTTAATTATGCTTATTATCTTTTG
GTTCTCACTTGAACTG CAA
GATCATAATGAAACTTGTCACG
CCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTC
ACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATG
ACCCGTGTCCTATTCACTTCTATTCTAA
ATG GTATATTAG AGTAG GAG CTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGG
CTGGTTCTAAATCACCCA
TTCAGTACATCGATATCG GTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTG CCAGGAACCTAAATTGG
GTAGTCTT
GTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACA
AAC
TAAAATGTCTGATAATGGACCCCAAAATCAG
CGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCA
GTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACTGCGTCTTG

GTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCG
AGGACAAGGCGTTCCAATTAACACCAATAGCAG
TCCAGAT GACCAAATTG G CTACTACCGAAG AG CTACCAGACGAATTCGTG GTG GTG ACG
GTAAAATGAAAG ATCTCAGTC
CAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATG
G
GTTG CAACTG AG G G AG CCTTGAATACACCAAAAG ATCACATTG G CACCCG CAATCCTG CTAACAATG
CTG CAATCGTG CT
ACAACTTCCTCAAG GAACAACATTG CCAAAAG G CTTCTACGCAGAAG G GAG CAGAG G CGG
CAGTCAAGCCTCTTCTCGTT
CCTCATCACGTAGTCG CAACAGTTCAAGAAATTCAACTCCAGGCAG CAG TAG G G GAACTTCTCCTGCTAG
AAT G G CTG GC
AATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCC
A
ACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGG
CTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTA
AAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAAT
C
AGACAAGG
AACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCGGAATGTCGCGC
ATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATT
T
CAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAA
A
AGAAGAAGGCTGATGAAACTCAAG
CCTTACCGCAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTGCAGAT
TTGGATGATTTCTCCAAACAATTG CAACAATCCATGAG CAGTGCTGACTCAACTCAG
GCCTAAACTCATGCAGACCACACA
AGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTA
ACT
ACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAG G G AG
GACTTG AAA
GAG CCACCACATTTTCACCGAG GCCACGCGGAGTACGATCGAGTGTACAGTGAACAATG CTAG G GAG
AGCTGCCTATAT
G GAAG AG CCCTAATGTGTAAAATTAATTTTAGTAGTG CTATCCCCATGTGATTTTAATAG CTTCTTAG GAG
AATG ACAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAA
SEQ ID NO: 2 Severe acute respiratory syndrome coronavirus 2 orf1ab polyprotein of isolate Wuhan-Hu-1 (GenBank:
OH D43415) M ESLVPG FN E KT H VQLSLPVLQVR DVLVRG FG DSVE EVLSEARQH LK DGTCG
LVEVEKGVLPQLEQPYVF I KRSDARTAP HG H
VMVELVAELEGIQYGRSG ETLGVLVP HVG El PVAYRKVLLRKNG NKGAGG HSYGADLKSFDLG
DELGTDPYEDFQENWNTKH
SSGVTRELM RELNGGAYTRYVDNNFCGPDGYPLECIKDLLARAG KASCTLSEQLDF I DTKRGVYCCRE HER
EIAWYTERSEKSYE
LQTP FEIK LAKKF DTF NG E CP N FVFP LNSI I KT I QPRVE KKKLDG F M G RI
RSVYPVASPN ECNQMCLSTLM KC DHCG ETSWQTG
DFVKATC EFCGTEN LTKEGATTCGYLPQNAVVKIYCPACH NSEVG P EHSLAEYH NESGLKTI LRKGG
RTIAFGGCVFSYVGCHNK

LASFSASTSAFVETVKGLDYKAF KQIVESC
G N F KVTKGKAKKG AWN IG EQKSI LSPLYAFASEAARVVRS I FSRTLETAQNSVRVLQKAAITI LDG
ISQYSLRL I DAM M FTSDLAT

NN LVVMAYITGGVVQLTSQWLTN I FGTVYE KLKPVLDWL EE KF KEG VEF LR DGWEIVKFISTCAC
EIVGG QIVTCAKE I KESVQT
F FKLVNKFLALCADSI I IGGAKLKALNLGETFVTHSKGLYRKCVKSREETG LLMP LKAPKE I I F LEG
ETLPTEVLTEEVVLKTG DLQP L
EQPTSEAVEAPLVGTPVC I NGLM LLE I KDTEKYCALAPNM MVTNNTFTLKGGAPTKVTFG DDTVI
EVQGYKSVN ITF E LDER I DK
VLNEKCSAYTVELGTEVNEFACVVADAVIKTLQPVSELLTPLG I DLDEWSMATYY LF DESG EF KLASH
MYCSFYP P DED EEEG DC
EEEEF EPSTQYEYGTEDDYQGKP LE FGATSAALQPEEEQEEDWLDDDSQQTVGQQDGSE
DNQTTTIQTIVEVQPQLEM [LIP
VVQTI EVNSFSGYLKLTDNVYIKNADIVEEAKKVK PTVVVNAAN VYLKHGGGVAGALN KATN NAM QVESD
DYIAT NG P LKVG
GSCVLSGHNLAKHCLHVVG PNVNKG EDIQLLKSAYENF NQH EVLLAPLLSAG I FGADPI HS
LRVCVDTVRTNVYLAVF DKN LYD
KLVSSFLEM KSEKQVEQKIAEIPKEEVKP FITESKPSVEQRKQDDKKIKACVEEVTTTLEETKFLTENLLLYI
DING NLHPDSATLVSD
I DITF LK KDAPYIVG DVVQEGVLTAVVI PTKKAGGTTEM LAKALRKVPTDNYITTYPGQG LNG
YTVEEAKTVLKKCKSAFYILPSI IS
NEKQEI LGTVSWN LREMLAHAEETRKLM
PVCVETKAIVSTIQRKYKGIKIQEGVVDYGARFYFYTSKTIVASLINTLN DLN ETLVT
M PLGYVTHGLN LE EAARYM RSLKVPATVSVSSP DAVTAYNGYLTSSSKTPE EH Fl ETISLAGSYKDWSYSG QSTQLG I E FLKRG D
KSVYYTSNPTTFHLDGEVITFDNLKTLLSLREVRTIKVFTTVDN IN LHTQVV DMSMTYGQQFG
PTYLDGADVTKI KPH NSH EG KT
FYVLPNDDTLRVEAFEYYHTTDPSF LGRYMSALN HTKKWKYPQVNGLTSIKWADNNCYLATALLTLQQI
ELKFNPPALQDAYYR
ARAGEAAN FCALI LAYCNKTVGE
LGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQFKKGV
QIPCTCGKQATKYLVQQESPFVM MSAPPAQYELKHGTFTCASEYTGNYQCGHYKHITSKETLYCI
DGALLTKSSEYKGPITDVFY
KENSYTTTI KPVTYKLDGVVCTEI DP KLD NYYKKDNSYFTEQPI DLVP NQPYPNASF DN F KFVCD NI
KFADDLNQLTGYKKPASRE
LKVTFF PDLNGDVVAIDYKHYTPSF KKGAKLLH
KPIVWHVNNATNKATYKPNTWCIRCLWSTKPVETSNSFDVLKSEDAQGM D
N LACEDLKPVSE EVVEN PTIQKDVLEC NVKTTEVVG D I I LKPA NNS LKITE EVG
HTDLMAAYVDNSSLTI KKPN E LSRVLG LKTLAT
HGLAAVNSVPWDTIANYAKPFLNKVVSTTTNIVTRCLNRVCTNYM PYFFTLLLQLCTFTRSTNSR I KASM
PTTIAKNTVKSVGKF
CLEASF NYLKSP N FSKLI NI I IWF LLLSVCLGSLIYSTAALGVLMSN LGM PSYCTG YR
EGYLNSTNVTIATYCTGSI PCSVCLSGLDSL
DTYPSLETIQITISSFKWDLTAFGLVAEWFLAYILFTRFFYVLGLAAIMQLFFSYFAVH F ISNSWLMWLI I
NLVQMAPISAM VR MY
IF FASFYYVWKSYVHVVDGCNSSTCM MCYKR NRATRVECTTIVNGVR RSFYVYANGG KG FCKLH
NWNCVNCDTFCAGSTF IS
DEVARDLSLQFKRPI NPTDOSSYIVDSVTVKNGSIHLYFDKAGQKTYER HSLSH FVN LDN LRAN NT KGSLP
INVIVFDG KSKCE ES
SAKSASVYYSQLMCQP I LLLDQA LVSDVG DSAEVAVK M FDAYVNTFSSTFNVPME
KLKTLVATAEAELAKNVSLDNVLSTF ISAA
RQGFVDSDVETKDVVECLKLSHQSDI EVTGDSCNNYMLTYN KVENMTP RDLGACI DCSAR H I NAQVAKSH
NIALIWNVKDF M
SLSEQL R1(01 RSAAKKN NLPFKLICATTRQVVNVVITKIALKGGKIVNNWLKQLIKVTLVFLFVAA1 FYLITPVHVMSKHTDFSSEI I
GYKAI DGGVTR DIASTDTC FAN K HADFDTW FSQRGGSYTNDKAC P LIAAVITREVG FVVPG
LPGTILRTTNGD F LH FLPRVFSAV
GNICYTPSKLI EYTDFATSACVLAAECTIF KDASGKPVPYCYDTNVLEGSVAYESLRPDTRYVLM DGSI I QF
P NTY LEGSVRVVTTF
DSEYCRHGTCERSEAGVCVSTSG RWVLNNDYYRSLPGVFCGVDAVNLLTN M FTPLIQP
IGALDISASIVAGGIVAIVVTCLAYYF
M RF RRAFG EYSHVVAF NTLLF LMSFTVLCLTPVYSF LPGVYSVIYLYLTFYLTNDVSF LAH I QW M VM
FTPLVPFWITIAYIICISTK
HFYWF FSNYL KR RVVFNGVSFSTFEEAALCT F LLN KE MYLKLRSDVLLP
LTQYNRYLALYNKYKYFSGAMDTTSYREAACCH LAK
ALN DFSNSGSDVLYQPPQTSITSAVLQSG F RKMAF PSG KVEGC M VQVTCGTTTLNG
LWLDDVVYCPRHVICTSEDM LNP NYE
DLLIRKSN HNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTP KYKFVR IQPGQTFSVLACYNGSPSGVYQCAM
RP NFTI KG
SF LNGSCGSVG F NI DYDCVSFCYM H H M ELPTGVHAGTDLEG NI FYG PFVDRQTAQAAGTDTTITVN
VLAW LYAAVI NG DRWF
LNRFTTTLNDFN LVAMKYNYE PLTQDHVDILG PLSAQTGIAVLDMCASLKE LLQNGM NG RTILGSALLE DE
FTP F DVVRQCSGV
TFQSAVKRTI KGTHHWLLLTILTSLLVLVQSTQWSLFF F LYE NAF LPFAMG IIAMSAFAM M
FVKHKHAFLCLFLLPSLATVAYFN
MVYMPASWVM RI MTWLDMVDTSLSGF KLKDCVMYASAVVLLILMTARTVYDDGARRVWTLM NVLTLVYKVYYG
NALDQA
ISMWALIISVTSNYSGVVTTVMF LARGIVF M CVEYC PI FFITGNTLQCIMLVYCFLGYFCTCYFGLFCLLN
RYFRLTLGVYDYLVST
QEF RYM NSQG LLPPKNSI DAF KLN I KLLGVGGKPCI
KVATVQSKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHN DI LLA
KDTTEAFE KM VSLLSVLLSM QGAV DI N KLCEEMLDN RATLQAIASEFSSLPSYAAFATAQEAYEQAVANG
DSEVVLKKLKKSL N
VAKSE F DR DAAM QRKLEKMADQAMTQMYKQARSED KRAKVTSAM QTM LFTM LRKLDN DALN NI I N
NAR DGCVPLN I IP LT
TAAKLMVVI PDYNTYKNTCDGTTFTYASALWEIQQVVDADSKIVQLSEIS M
DNSPNLAWPLIVTALRANSAVKLQNN ELSPVAL
RQMSCAAGTTQTACTDDNALAYYNTTKGG R FV LALLSDLQDL KWAR F PKSDGTGTIYTELE
PPCRFVTDTPKG P KVKYLYFI KG
LNNLNRG MVLGSLAATVRLQAG NATEVPANSTVLSFCAFAVDAAKAYKDYLASGGQPITNCVKM
LCTHTGTGQAITVTPEAN
M DQESFGGASCCLYCRCH IDH P NPKGFCDL KG KYVQI PTTCANDPVG FTLKNTVCTVCG
MWKGYGCSCDQLR EP M LQSADA
QSFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKTNCCRFQEKDEDDN LI DSYFVVKR
HTFSNYQHE ETIYN L
LKDCPAVAKH DFFKF RI DG DMVPH ISRQRLTKYTM ADLVYALR H F DEGNCDTLKE I LVTYNCC DD
DYF N KKDWYDFVEN PD IL
RVYANLG E RVRCIALLKTVQFC DAM R NAG IVGVLTLDNQDLNGNWYDFG DF IOTTPGSG
VPVVDSYYSLLM PI LTLTRALTAES
HVDTDLTKPYIKWDLLKYDFTEERLKLFDRYFKYWDQTYHPNCVNCLDDRCILHCANFNVLFSTVFPPTSFGPLVRKIF
VDGVPF
VVSTGYH FRELGVVHNQDVN LHSSRLSFKELLVYAADPAM HAASGNLLLDKRTTCFSVAALTN
NVAFQTVKPGNF N KDFYD FA
VSKG FFKEGSSVELKHFFFAQDG NAAISDYDYYRYN LPTMCDIRQLLFVVEVVDKYFDCYDGGCI NA NQVIVN
NLDKSAGFPFN
KWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMN LKYAISAKNRARTVAGVSICSTMTNRQF
HQKLLKSIAATRGATVVIGT
SKFYGGWH NM LKTVYSDVEN PH LM GWDYP KC DRAM PNM LR I
MASLVLARKHTTCCSLSHRFYRLANECAQVLSEMVMCG
GSLYVKPGGTSSGDATTAYANSVFNICQAVTANVNALLSTDGNKIADKYVRNLQH
RLYECLYRNRDVDTDFVNEFYAYLRKH FS
MM I LSDDAVVC F NSTYASQGLVASI KN FKSVLYYQNNVFMSEAKCWTETDLTKGPH EFCSQHTM LVKCIG
DDYVYLPYP DPSR I

LGAGCFVDDIVKTDGTLM I E RFVSLAI DAYPLTKH P NQEYADVF H LYLQYI RKLH DE LTG HM
LDMYSVM LTNDNTSRYWEPEF
YEAMYTPHTVLQAVGACVLCNSQTSLRCGACI RRPFLCCKCCYDHVISTSHKLVLSVN
PYVCNAPGCDVTDVTQLYLGGMSYYC
KSHKPPISFPLCANGQVFGLYKNTCVGSDNVIDFNAIATCDVVINAGDYI
LANTCTERLKLFAAETLKATEETFKLSYGIATVREVL
SDRE LH LSWEVG K P RP PL NRNYVFTGYRVTKNSKVQIG EYTF EKG DYG
DAVVYRGTITYKLNVGDYFVLISHTVM PLSAPTLVP
QEHYVRITGLYPTLNISDEFSSNVANYQKVG MQKYSTLQG PPGTG KSHFAIG
LALYYPSARIVYTACSHAAVDALCEKALKYLPID
KCSRI I PARARVECF D KFKVNSTLEQYVFCTVNAL PETTADIVVF DE ISMATNYDLSVVNAR
LRAKHYVYIG DPAQLPAPRTLLTK
GTLEPEYFNSVCRLM KTIG P DM F LGTCRRCPAEIVDTVSALVYDN KLKAHKDKSAQCFKM
FYKGVITHDVSSAINRPQIGVVREF
LTRNPAWRKAVFISPYNSQNAVASKI LG LPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKVG I
LCI MSDRDLYDK
LQFTSLEIPRRNVATLQAENVTG LFKDCSKVITGLHPTQAPTHLSVDTKFKTEG LCVDI
PGIPKDMTYRRLISMMG F KM NYQVN
GYPNM FITREEAIRHVRAWIG FDVEGCHATREAVGTNLPLQLG FSTGVN LVAVPTGYVDTPN NT DFSRVSAK
PPPG DQFKH LI
PLMYKGLPWNVVRIKIVQM LSDTLKNLSDRVVFVLWAHG FELTSM
KYFVKIGPERTCCLCDRRATCFSTASDTYACWHHSIGF
DYVYNPF M I DVQQWG FTG NLQSNHDLYCQVHGNAHVASCDAI MTRCLAVHECFVKRVDWTI EYPI I G
DE LKI NAACRKVQH
MVVKAALLADKFPVLH DIGNPKAIKCVPQADVEWKFYDAQPCSDKAYKI
EELFYSYATHSDKFTDGVCLFWNCNVDRYPANSI
VCRFDTRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFVN LKQLPFFYYSDSPCESHG
KQVVSDIDYVPLKSATCITRCNLGGA
VCRH HAN EYRLYLDAYN M M ISAG FSLWVYKQF DTYN LW NTFTRLQSLE NVAF NVVN KG H
FDGQQG EVPVSI I N NTVYTKVD
GVDVELF E NKTTLPVNVAF E LWAK RN IKPVPEVKI LN
NLGVDIAANTVIWDYKRDAPAHISTIGVCSMTDIAKKPTETICAP LTVF
FDGRVDGQVDLFRNARNGVLITEGSVKG LQPSVG PKQASLNGVTLIG
EAVKTQFNYYKKVDGVVQQLPETYFTQSRNLQEFKP
RSQM E I DF LELA M DEFI ERYKLEGYAFEHIVYGDFSHSQLGG LI-I LLIG LAKRF KESPF E LE
DF I PM DSTVKNYFITDAQTGSSKCVC
SVI DLLLD DFVE II KSQDLSVVSKVVKVTIDYTEISFM LWCKDG HVETFYPKLQSSQAWQPGVAMPN
LYKMQRMLLE KC DLQN
YGDSATLPKGI MM NVAKYTQLCQYLNTLTLAVPYNMRVI HFGAGSDKGVAPGTAVLRQWLPTGTLLVDSDLN
DFVSDADSTL I
G DCATVHTAN KW DLIISDMYDPKTKNVTKENDSKEGFFTYICG FIQQKLALGGSVAIKITEHSWNADLYKLMGH
FAWWTAFV
TNVNASSSEAFLIGCNYLG KPREQIDGYVMHANYIFWRNTN PIQLSSYSLFDMSKFPLKLRGTAVMSLKEGQI N
DM I LSLLSKG R
L I I REN NRVVISSDVLVNN
SEQ ID NO: 3 Severe acute respiratory syndrome coronavirus 2 surface glycoprotein (GenBank:
QHD43416) M FVF LVLLP LVSSQCVN LTTRTQLP PAYTNSFTRGVYYPDKVF RSSVLHSTQDLF LP FFSNVTWF HAI
HVSGTNGTK RF DN PVLP
F N DGVYFAST EKSN II RG WIFGTTLDSKTQSLLIVN NATNVVI KVCE FQFCN DP FLGVYYHK N N
KSWM ESE F RVYSSAN NCTF EY
VSQPF LM DLEGKQG NFKN LRE FVF KN I DGYFKIYSKHTP I N LVR DLPQG FSALEP LVDLPIG I
NI ITRFQTLLALH RSYLTPG DSSSG
WTAGAAAYYVGYLQPRTFLLKYNE
NGTITDAVDCALDPLSETKCILKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFN
ATRFASVYAWN RKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRG
DEVRQIAPGQTGKIADYNYKLPDD
FTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQP
YRVVV
LSFELLHAPATVCG PKKSTNLVKNKCVN FN F NG LTGTGVLTESN KKF LPFQQFG
RDIADTTDAVRDPQTLE I LDITPCSFGGVSVI
TPGTNTSNQVAVLYQDVNCTEVPVAIHADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQ
TNSP
RRARSVASQSIIAYTMSLGAENSVAYSN NSIAIPTNFTISVTTE I LPVSMTKTSVDCTMYICG
DSTECSNLLLQYGSFCTQLNRALT
G IAVEQD KNTQEVFAQVKQIYKTP PI KDFGG F NFSQILP DPSKPSKRSFI E DL LF N KVTLADAG
FIKQYG DCLGDIAARDLICAQKF
NG LTVLPPL LTDEM IAQYTSALLAGTITSGWTFGAGAALQI PFAMQMAYRF NG
IGVTQNVLYENQKLIANQFNSAIG KIQDS LS
STASALG KLQDVVNQNAQALNTLVKQLSSN FGAISSVLN D I LSR LDKVEA EVQI D RLITG R
LQSLQTYVTQQLIRAAEI RASAN LA
ATKMSECVLGQSKRVDFCG KGYHLMSFPQSAPHGVVF LHVTYVPAQEKNFTTAPAICHDG KAH FP
REGVFVSNGTHWFVTQ
RNFYEPQIITTDNTFVSG NCDVVIG IVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISG I
NASVVNIQK El DRLNEVAKN
LNESLI DLQELGKYEQYIKWPWYIWLGFIAGLIAIVMVTIM
LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
SEQ ID NO: 4 CpG 1018 TGACTGTGAACGTTCGAGATGA
SEQ ID NO: 5 KLK peptide KLKLLLLLKLK
SEQ ID NO: 6 Oligo-d(IC)13 (ODN1a) ICICICICICICICICICICICICIC
SEQ ID NO: 7 CpG 1826 TC CATG ACGTTCCTG ACG TT
SEQ ID NO: 8 CpG 7909 TC GTCG TTTTGTCGTTTTG TCG TT
SEQ ID NO: 9 >hCoV-19/Ita ly/INM11-is1/20201EPLISL_410545 I 2020-01-29 (Accession No:
M1066156) ATTAAAGGTTTATACCTTCCCAGGTAACAAACCAACCAACTTTCGATCTCTTGTAGATCTGTTCTCTAAACGAACTTTA
AAA
TCTGTGTGG CTGTCACTCGGCTGCATGCTTAGTGCACTCACG
CAGTATAATTAATAACTAATTACTGTCGTTGACAG GACA
CGAGTAACTCGTCTATCTTCTGCAGG CTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAG CACATCTAG
GTTTCGTCC
GG GTG TG ACC G AAAG GTAAG ATG G AG AG CCTTGTCCCTG G TTTCAACG AG
AAAACACACGTCCAACTCAG TTTG CCTG TT
TTACAGGTTCGCGACGTG CTCGTACGTG G CTTTG GAGACTCCGTGGAG GAG GTCTTATCAGAG
GCACGTCAACATCTTAA
AGATGG CACTTGTG GCTTAGTAGAAGTTGAAAAAG G CGTTTTG C CTCAACTTG AACAG CC CTATG
TGTTCATCAAACGTTC
GGATG CTCGAACTGCACCTCATGGTCATGTTATG GTTG AG CTG GTAGCAGAACTCGAAG G CATTCAGTACG
GTCGTAGTG
GTGAGACACTTGGTGTCCTTGTCCCTCATGTGG G CGAAATACCAGTGGCTTACCG CAAG
GTTCTTCTTCGTAAGAACGGTA
ATAAAG G AG CTG GTGGCCATAGTTACG GCG CCGATCTAAAGTCATTTG ACTTAG GC GACG AG CTTG
G CACTGATCCTTAT
GAAGATTTTCAAGAAAACTGGAACACTAAACATAG CAGTGGTGTTACCCGTGAACTCATG CGTGAG CTTAACG G
AG GG G
CATACACTCG CTATGTCGATAACAACTTCTGTG G CC CTG ATG
GCTACCCTCTTGAGTGCATTAAAGACCTTCTAG CACGTGC
TG GTAAAGCTTCATG CACTTTGTCCGAACAACTG GACTTTATTG ACACTAAG AG G G GTGTATACTG CTG
CCGTG AACATG A
GCATGAAATTGCTTG GTACACG G AACGTTCTG AAAAG AG CT ATG AATTG
CAGACACCTTTTGAAATTAAATTG GCAAAGA
AATTTGACACCTTCAATGG GGAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGG
GTTGA
AAAGAAAAAG CTTG ATG GCTTTATGG
GTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGT
GCCTTTCAACTCTCATGAAGTGTGATCATTGTG GTGAAACTTCATGGCAGACGGG CGATTTTGTTAAAG
CCACTTGCGAAT
TTTGTG G CACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTG GTTACTTACCCCAAAATG
CTGTTGTTAAAATTTATTG
TCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATT
CT
TCGTAAG GGTG GTCGCACTATTG CCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTG CCATAACAAGTGTG
CCTATTG G GT
TCCACGTGCTAG CGCT AACATAGGTTGTAACCATACAG GTGTTG TTG G AG AAG GTTCCGAAG
GTCTTAATGACAACCTTCT
TG AAATACTC CAAAAAG AG AAAG TCAACATCAATATTGTTG GTGACTTTAAA CTTAATG AAGAG ATCG
CCATTATTTTG G C
ATCTTTTTCTGCTTCCACAAGTG CTTTTGTGGAAACTGTGAAAGGTTTGG ATTATAAAG
CATTCAAACAAATTGTTGAATCC
TGTGGTAATTTTAAAGTTACAAAAG GAAAAGCTAAAAAAGGTGCCTG
GAATATTGGTGAACAGAAATCAATACTGAGTCC
TCTTTATGCATTTG CATCAG AG G CTG CTC G TG TTG TACG ATCAATTTTCTCC CG CACTCTTG
AAACTG CTCAAAATTCTGTGC
GTGTTTTACAGAAGGCCG CTATAACAATACTAGATG GAATTTCACAGTATTCACTGAGACTCATTG ATG
CTATGATGTTCA
CATCTGATTTG GCTACTAACAATCTAGTTGTAATGG
CCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGG CTAA
CTAACATCTTTG GCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGG CTTGAAGAGAAGTTTAAGGAAG
GTGTAGAGT
TTCTTAGAGACGGTTG GGAAATTGTTAAATTTATCTCAACCTGTG
CTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTG
CTAAG G AAATTAAG G AG AGTG TTCAG ACATTCTTTAAG CTTGTAAATAAATTTTTGGCTTTGTGTG
CTGACTCTATCATTAT
TG GTG G AG CTAAACTTAAAG CCTTGAATTTAGGTGAAACATTTGTCACG CACTCAAAG
GGATTGTACAGAAAGTGTGTTA
AATCCAG AG AAG AAACTG G CCTACTCATG CCTCT AAAAG CCCCAAAAG AAATTATCTTCTTAG AG G
G AG AAACACTTCC CA
CAG AAGTGTTAACAG AG GAAGTTGTCTTGAAAACTG GTGATTTACAACCATTAGAACAACCTACTAGTGAAG
CTGTTG AA
GCTCCATTGGTTG GTACACCAGTTTGTATTAACGGG CTTATGTTG
CTCGAAATCAAAGACACAGAAAAGTACTGTG CCCTT
GCACCTAATATGATGGTAACAAACAATACCTTCACACTCAAAG GCG GTG
CACCAACAAAGGTTACTTTTGGTGATGACACT
GTGATAGAAGTGCAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAG G ATTG
ATAAAGTACTTAATG AG AA
GTGCTCTGCCTATACAGTTGAACTCGGTACAGAAGTAAATGAGTTCG CCTGTGTTGTGG
CAGATGCTGTCATAAAAACTTT
GCAACCAGTATCTGAATTACTTACACCACTGGG CATTGATTTAGATGAGTGGAGTATG
GCTACATACTACTTATTTGATGA
GTCTGGTGAGTTTAAATTG G CTTCACATATGTATTG TTCTTTCTACCCT CCAG ATG AG G ATG AAG AAG
AAG G TG ATTG TG A
AGAAG AAG AGTTTG AG CCATCAACTCAATATGAGTATG GTACTGAAG ATGATTACCAAG
GTAAACCTTTGGAATTTG GTG
CCACTTCTG CTG CTCTTCAACCTG AAG AAG AG CAAG AAG AAG ATTG
GTTAGATGATGATAGTCAACAAACTGTTGGTCAA
CAAGACGG CAGTG AG G ACAATCAG ACAACTACTATTCAAACAATTGTTG AG GTTCAACCTCAATTAG AG
ATG G AACTTAC
ACCAGTTGTTCAGACTATTGAAGTG AATAG TTTTAGTG GTTATTTAAAACTTACTG ACAATG
TATACATTAAAAATG CAG A
CATTGTG GAAGAAG CTAAAAAG GTAAAACCAACAGTG GTTGTTAATG CAG CCAATGTTTACCTTAAACATG
GAG GAGGT
GTTGCAG GAG CCTTAAATAAG GCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAG CTACTAATG
GACCACTT
AAAGTGG GTGGTAGTTGTGTTTTAAG CGGACACAATCTTG
CTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAA
GGTGAAGACATTCAACTTCTTAAGAGTG CTTATGAAAATTTTAATCAG CAC G AAGTTCTACTTG
CACCATTATTATCAGCTG

GTATTTTTG GTG CTG AC CCTATACATT CTTTAAG AG TTTG TG TAG ATACTG TTC G
CACAAATGTCTACTTAG CTG T CTTTG AT
AAAAATCTCTATG A CAAACTTG TTTCAAG CTTTTTG GAAATG AAG AG T G AAAAG CAA G TTG
AACAAAAGATCG CTG AG AT
TCCTAAAG AG G AAGTTAAG C C ATTTATAACTG AAA G TAAA CCTT CAG TTG AAC AG AG
AAAACAAG ATG ATAAG AAAAT CA
AAG CTTG TG TTG AAG AAG TTACAACAACT CT G G AAG AAACTAA G TT CCTCAC AG AAAACTT
G TTACTTT ATATTG ACATTA
ATG G CAATCTTCATCCAGATTCTG CCACTCTIG TTAG T G AC ATTG AC ATCA CITT CTTAAAG AAA
G ATG CTCCATATATAGT
G G GTG ATG TUG TT CAAG AG G GTGTTTTAACTG CTGTG GTTATACCTACTAAAAAG G CT G GTG
G CACTACTG AAATG CTAG
CG AAAG CTTTG AG AAAA GTG CCAACAGACAATTATATAACCACTTACCCG G GTC AG G GTTTAAATG
GTTA CACTG TAG AG
GAG G CAAAGACAGTG CTTAAAAAGTGTAAAAGTG CCTTTTACATTCTACCATCTATTATCT CTAATG AG
AAG CAAG AAATT
CTTG GAACTGTTTCTTG GAATTTG CG AG AAATG CTTG CACATG CAG AAG AAACACG CAAATTAATG
C CTG TCTG TGTG G A
AACTAAAG CCATAGTTTCAACTATACAG CGTAAATATAAG G G TATTAAAATACAAG AG G GTGTGG TTG
ATTATG GTG CTA
G ATTTTACTTTTACACCAGTAAAACAACTG TAG
CGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAAT
G CCACTTG G CTATGTAACACATG G CTTAAATTTG GAAG AAG CTG CT C G G TAT ATG A G ATCT
CTC AAAG TG CCAG CTACAGT
TT CTG TTTCTTCACCTG AT G CTG TTAC AG CGTATAATG
GTTATCTTACTTCTTCTTCTAAAACACCTGAAG AACATTTTATTG
AAACCATCTCACTTG CT G GTTCCTATAAAG ATTG GTCCTATTCTG GACAATCTACACAACTAG GTATAG
AATTT CTTAAG AG
AG G TG ATAAAAG TG TATATTACACTAG TAATCCTACCAC ATTC CA CCTAG ATG G
TGAAGTTATCACCTTTG AC AATCTTAAG
ACACTTCTTTCTTTGAG AG AAGTG AG GACTATTAAG GTG TTTACAACAG TAG
ACAACATTAACCTCCACACG CAA GTTGTG
G AC ATG T CAATG ACATATG G ACAACAGTTTG G TC CAA CTTATTTG GATG GAG CTG
ATGTTACTAAAATAAAACCTCATAAT
TCACATG AAG GTAAAACATTTTATGTTTTACCTAATGATGACACTCTACG TGTTG AG G CTTTTG AG
TACTAC CACACAACTG
ATCCTAGTTTTCTG G GTAG GTACATGTCAG CATTAAATCACACTAAAAAGTG GAAATACCCACAAGTTAATG
GTTTAACTT
CTATTAAATG G G CAG ATAACAACTGTTATCTTG CCACTG CATTG TTAACA CTC CAACAAATAG AG
TTG AAGTTTAAT CCA CC
TG CT CTACAAG AT G CTTATTACAG AG CAAG G G CTG GTGAAG CTG CTAACTTTTGTG CA CTTAT
CTTA G CCTACTG TAATAA
G AC AG TAG GTG AG TTAG GTGATGTTAG AG AAAC AAT G A G TTA CTTGTTTCAACATG
CCAATTTAG ATTCTTG CAAAAG AG
TCTTG AA C G TG GTGTGTAAAACTTGTG G ACAACAG C AG ACAA CCCTTAAG G G TG TA G AA G
CTGTTATGTACATG G G CAC A
CTTTCTTATG AACAATTTAAG AAA G G TG TT CAG ATACCTTG TAC G TG TG G TAAAC AA G
CTACAAAATATCTAGTACAACAG
G AG TCA CCTTTTG TTATG ATG TC AG CAC CACCT G CT CAG TATG AA CTTAA G CAT G G TA
CATTTACTT G TG CTAG TG AG TACA
CTG GTAATTACCAGTGTG GTCACTATAAACATATAACTTCTAAAG AAACTTTG TATTG CATAG AC G GTG
CTTTACTTACAAA
G T CCTC A G AATAC AAAG GTCCTATTACG G AT G TTTT CTA CAAAG AAAACAG TTACA CAACAA
CCATAAAACCA G TTA CTTA
TAAATTG GATG GTG TTGTTTGTACAG AAATTG AC CCTAAG TTG G ACAATTATTATAAG AAAG
ACAATT CTTATTTC A CAG A
G C AACCAATTG AT CTT G TAC C AAAC CAAC CATATC CAAAC G CAAG CTTCG ATAATTTTAAG
TTT G TAT G TG ATAATATCAAA
TTTG CT G ATG ATTTAAACCAGTTAACTGGTTATAAG AAACCTG CTTCAA G AG AG
CTTAAAGTTACATTTTTCCCTG ACTTAA
ATG GTG ATGTG GTG G CTATTG ATTATAAACACTA CAC ACC CTCTTTTAAGAAAG GAG
CTAAATTGTTACATAAACCTATTG
TTTGG CATGTTAACAATG CAACTAATAAAG CCACGTATAAACCAAATACCTG G TG TATAC G TT
GTCTTTG GAG CACAAAAC
CAGTTG AAACAT CAAATT C G TTTG ATG TA CTG AA G TCAG AG G AC G C G CAG G GAATG
GATAATCTTG CCTGC GAAGATCTA
AAACCAGTCTCTG AAG AAG TAG TG G AAAATCCTAC CATAC AG AAAG AC GTT CTTG AG TG TAAT
G TG AAAACTACCGAAGT
TG TAG G AG ACATTATACTTAAACCAG CAAATAATAGTTTAAAAATTACAG AAG AG GTTG G CCACACAG
ATCTAATG G CTG
CTTATG TAG A CAATT CTAG TCTTACTATTAAG AAACCTAATG AATTATCTAG AG TATTAG GTTTG
AAAACCCTTG CTACTCA
TG GTTTAG CT G CT G TTAATAG T G TC CCTTG G GATACTATAG CTAATTATG CTAAG
CCTTTTCTTAACAAAGTTGTTAGTACA
ACTACTAACATAG TTACACG GTGTTTAAACCGTGTTTGTACTAATTATATG CCTTATTTCTTTACTTTATTG
CTACAATTGTG
TACTTTTACTAG AAGTACAAATTCTAGAATTAAAG C ATCTATG CC G ACTACTATAG
CAAAGAATACTGTTAAG AG TG TC G G
TAAATTTTG TCTAG AG G
CTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATTTG GTTTTTACT
ATTAAGTGTTTG CCTAG G TTCTTTAAT CTACTCAA CC G CTG CTTTAG GTGTTTTAATGTCTAATTTAG
G CATG CCTTCTTACT
GTACTG G TTA CAG AG AA G G CTATTTGAACTCTACTAATGTCACTATTG CAACCTACTGTACTG G TT
CTATA CCTT G TAG TG T
TT G TCTTAG TG GTTTAG ATTCTTTAGACACCTATCCTTCTTTAGAAACTATACAAATTAC
CATTTCATCTTTTAAATG G GATTT
AACTGCTTTTG G CTTAGTTG CAGAGTG GTTTTTG G CATATATTCTTTTCACTAG GTTTTTCTATGTACTTG
GATTG G CTG CAA
TCATG CA ATTG TTTTTCAG CTATTTTG CAGTACATTTTATTAGTAATTCTTG G CTTATGTG
GTTAATAATTAATCTTGTACAA
ATG G CCCCGATTTCAG CTATG GTTAGAATGTACATCTTCTTTG CATCATTTTATTATGTATG
GAAAAGTTATGTGCATGTTG
TAG ACG G TTG TAATT C ATC AACTT G TAT G ATG TG TTACAAA C G TA ATA G AG CAAC
AAG AG T C G AATG TAC AACTATTG TTA
ATG GTGTTAG AAG GTCCTTTTATGTCTATG CTAATG G AG GTAAAG G CTTTTG CAAACTACACAATTG
GAATTGTGTTAATT
GTGATACATTCTGTG CTG G TA G TACATTTATTAG TG AT G AAGTTG C G AG AG ACTTG T
CACTACAG TTTAAAAG AC CAATAA
ATC CTACTG A CCAGTCTTCTTACATCGTT GATAGTGTTACAGTG AAG AATG
GTTCCATCCATCTTTACTTTG ATAAAGCTGG
TCAAAAGACTTATGAAAG ACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTG AGA G CTA ATAA CA
CTAAAG GTTCATTG
CCTATTAATGTTATAGTTTTTG ATG GTAAATCAAAATGTG AAGAATCATCTGCAAAATCAG
CGTCTGTTTACTACAGTCAG C
TTATGTGTCAACCTATACTGTTACTAGATCAG G CATTAG TG TCT G ATG TT G GTGATAGTG CG G
AAGTTG CAGTTAAAATGT
TT G ATG CTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATG GAAAAACTCAAAACACTAGTTG
CAACTG CAG AAG C
TG AACTTG CAAA G AATG TG T CCTTAG AC AAT G TCTTAT CTACTTTTATTT CA G CA G CTCGG
CAAG G GTTTGTTG ATTCA G AT

G TAG AAACTAAAG ATGTTGTTGAATGTCTTAAATTGTCACATCAATCTG AC ATA G AAG TTACTG G
CGATAGTTGTAATAAC
TATATG CTCACCTATAACAAAGTTGAAAACATGACACCCCGTGACCTTG GTG CTTGTATTG ACTGTAGTG CG
CGTCATATT
AATG CG C AG G T AG CAAAAAGTCACAACATTG CTTTGATATG G AA C G TTAAA G ATTTCAT G
TCATTG T CTG AACAACTAC G A
AAAC AAATA C G TA G TG CTG CTAAAAAGAATAACTTACCTTTTAAGTTGACATGTG CAACTACTAG
ACAAG TT G TTAAT G TT
GTAACAACAAAGATAG CACTTAAGG GTG GTAAAATTGTTAATAATTG G TTG AA G
CAGTTAATTAAAGTTACACTTGTGTTC
CTTTTTGTTG CTG CTATTTTCTATTTAATAA CACCT G TT CATG TCATG TCTAAACATACTG A
CTTTTCAAG TG AAATCATAG G
ATACAAG G CTATTGATG GTG GTGTCACTCGTG ACATAG CATCTACAG ATACTTGTTTTGCTAACAAACATG
CTGATTTTG A
CAC ATG GTTTAG CCAG CGTG GTG GTAGTTATACTAATGACAAAG CTTG CCCATTGATTG CTG CAG
TCATAACAAG AG AAG
TG G GTTTTGTCGTG CCTG GTTTG CCTG G CACGATATTACG CACAACTAATG GTG ACTTTTTG
CATTTCTTACCTAG AG TTTT
TAG TG CAGTTG GTAACATCTG TTACACAC CATC AAAACTTATAG AG TA CACTG ACTTTG
CAACATCAG CTTGTGTTTTG G CT
G CTG AAT GTACAATTTTTAAAG AT G CTTCTGGTAAG CCAG TACCATATT G TTATG ATACCAATG TA
CTAG AAG GTTCTGTTG
CTTATG AAAGTTTACG CCCT G ACA CAC G TTATG TG CTCATG G AT G G CT CTATTATT
CAATTTCCTAA CAC CTACCTTG AAGG
TT CTG TTAG A G TG GTAACAACTTTTG ATTCT G AG TA CTG TAG G CAC G G CACTTG TG AAA
G ATC AG AAG CTG GTGTTTGTGT
ATCTACTAGTG G TA G ATG G GTACTTAACAATGATTATTACAGATCTTTACCAG G AG TTTTCTG TG G
TG TAG AT G CTG TAAA
TTTACTTACTAATATG TTTA CAC CA CTAATTCAAC CTATTG GTG CTTTG G ACATATC AG
CATCTATAG TAG CTG G TG GTATT
G TAG CTATC G TAG TAACAT G CCTTG CCTACTATTTTATG AG GTTTAG AAG A G CTTTTG GTG
AATACA G TCATG TAG TT G CCT
TTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTG
GTGTTTATTCTGTTAT
TTACTTG TACTTG AC ATTTTATCTTACT AATG AT G TTTCTTTTTTAG C AC ATATTCAG TG G ATGG
TTATG TT CACAC CTTTAG T
ACCTTTCTG GATAACAATTG CTTATATCATTTGTATTTCCACAAAG CATTTCTATTG G TTCTTTAG
TAATTACCTAAAG AG AC
GTGTAGTCTTTAATG GTGTTTCCTTTAGTACTTTTGAAGAAG CTG CG CTG TG CACC TTTTTG
TTAAATAAAG AAAT GTAT CT
AAAGTTG CG TA G TG ATG TG CTATTACCTCTTACG CAATATAATAG ATACTTAG CT CTTTATAATAAG
TA CAAGTATTTTAG T
G GAG CAATG GATACAACTAG CTACAG A G AAG CTG CTTG TT G TCATCTC G CAAAG G
CTCTCAAT G ACTT CAG TAACTC AG G
TTCTG ATG TTCTTTACC AACCACCAC AAAC CTCTATCA CCTC A G CT G TTTT G CAG AG TG
GTTTTAG AAAAATG G CATTCCCA
TCTG GTAAAGTTG AG G GTTGTATG GTACAAGTAACTTGTG GTACAACTACACTTAACG GTCTTTG
GCTTGATG AC G TAG TT
TACTGTCCAAG AC ATG TGATCTG CACCTCTG AAG AC ATG CTTAACCCTAATTATGAAG
ATTTACTCATTCGTAAGTCTAATC
ATAATTTCTTG G TAC AG G CTG G TAAT G TTC AACTC AG GGTTATTG GACATTCTATG CAAAATTG
TG TA CTTAA G CTTAAG G
TT G ATAC AG CC AATCCTAAG A CACCTAAG TATAAG TTTG TTC G CATTCAACCAG G AC AG
ACTTTTTCA G TG TTAG CTTGTTA
CAATGGTTCACCATCTG GTGTTTACCAATGTG CTAT G AG G CCCAATTTCACTATTAAGG G TT CATTC
CTTAATG GTTCATGT
G GTAGTGTTG GTTTTAACATAG ATTATGACTGTGTCTCTTTTTGTTACATG CACCATATGG AATTACCAACTG
G AG TTCATG
CTG G CAC AG ACTTAG AA G GTAACTTTTATG G ACCTTTTGTTG ACAG G CAAAC AG C AC AAG
CAG CTG GTACG GACACAACT
ATTACAGTTAATGTTTTAGCTTG GTTGTACG CTGCTGTTATAAATG G AG ACAG GTG GTTTCTCAATCG
ATTTACCACAACTC
TTAATG A CTTTAACCTTG TG G CTATG AA G TAC AATTATG AAC CTCTAACACAAG ACC ATG TT G
ACATACTAG GACCTCTTTC
TG CT CAA ACTG G AATT G CC GTTTTAG ATATGTGTG CTTCATTAAAAGAATTACTG CAAAATG
GTATGAATGG ACGTACCAT
AUG GGTAGTG CTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATG CTCAG
GTGTTACTTTCCAAAGTG CA
GTGAAAAG AACAATCAAGG GTACACACCACTG GTTGTTACTCACAATTTTGACTTCACTTTTAGTTTTAGTCCAG
AG TA CTC
AATG GT CTTT G TTCTTTTTTTT N TAT G AAAAT G CCTTTTTACCTTTTG CTATG G GTATTATTG
CTATGTCTGCTTTTG CAAT G A
TGTTTGTCAAACATAAG CAT G CATTTCTCTGTTTG TTTTTG TTACCTT CT CTT G CC ACTG TA G
CTTATTTTAATATG GTCTATA
TG CCTG CTAG TTG G GTGATG C GTATTATG AC ATG GTTG GATATG GTTGATACTAGTTTGTCTG
GTTTTAAGCTAAAAG ACT
GTGTTATGTATG CAT CAG CTGTAGTGTTACTAATCCTTATG ACAG CAAGAACTGTGTATG ATGATG GTG
CTAG G AG AGTG
TG GACACTTATGAATG TCTTGACACTCGTTTATAAAGTTTATTATG GTAATG CTTTAG ATCAAG
CCATTTCCATGTG G G CTC
TTATAATCTCTG TTACTTCTAACTA CTC AG G TG TAG TTACAACTG T CATG TTTTTG G CCAG A G
GTATTGTTTTTATG TG TG TT
G AG TATTG CCCTATTTTCTTCATAACTG GTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAG G
CTATTTTTG TACT
TGTTACTTTG G CCTCTTTTGTTTACTCAACCG CT ACTTTAG A CTG A CTCTTG GTGTTTATG
ATTACTTAGTTTCTACACAG G A
GTTTAG ATATATG AATTCAC AG GG ACTA CTCCCA CCCAAG AATAG CATAGATG
CCTTCAAACTCAACATTAAATTGTTG GG
TGTTG GTG G CAAACCTTGTATCAAAGTAG CC ACT G TA CAG T CTAAAATG T CAG AT G TAAAG
TG C ACATCAG TA G TCTTACT
CTC A G TTTTG CAACAACTCAG AG TA G AATC ATCAT CTAAATTGT G G G
CTCAATGTGTCCAGTTACACAATGACATTCTCTTA
G CTAAAG ATACTACTG AAG CCTTTG AAAAAATG GTTTCACTACTTTCTGTTTTG CTTTCCATG CAGG
GTG CTG TAG AC ATAA
ACAAGCTTTGTGAAG AAATG CTG GACAACAG G G CAA CCTTACAA G CTATAG CCTCAG AG TTTAG
TTCCCTTCC ATCATATG
CAG CTTTTG CTACTG CTCAAGAAG CTTATG AG CAGG CTGTTG CTAATG GTG ATTCTG AAG TTG
TTCTTAAAAA GTTG AAG A
AGTCTTTGAATGTG G CTAAATCTG AATTTG AC CGTG ATG CAG CCATG CAACGTAAGTTG GAAAAGATG
G CTGATCAAG CT
ATG ACCCA AATG TATA AAC AG G CTAG AT CTG AGGA CAAG AG G G CAAAAGTTACTAGTG
CTATG CAG ACAATG CTTTT CA C
TATG CTTAGAAAGTTG GATAATGATG CACT CAAC AACATTATCAAC AATG CAAG AG ATG
GTTGTGTTCCCTTGAACATAAT
ACCTCTTACAACAG CAG CCAAACTAATG G TTG TCATA CCAG A CTATAACAC ATATAAAAATAC G TG
TG ATG G TAC AA CATT
TACTTATG CAT CAG CATTGTG G G AAAT CCAAC AG G TTG TA G AT G CAG ATAG TAAAATT G
TTC AA CTTA G TG AAATTAG TAT
G GACAATTCACCTAATTTAG CATG G CCTCTTATTGTAACAG CTTTAAG GG CCAATTCTG CTG
TCAAATTACA G AATAATG A

G CTTAGTCCTGTTG CACTACGACAGATGTCTTGTG CTG CCG GTACTACACAAACTGCTTG CA CTG ATG
AC AATG CGTTAG C
TTACTACAACACAACAAAG G G AG GTAG GTTTGTACTTG CACTGTTATCCG ATTTACAG G ATTTGAAATG
G G CTAGATTCCC
TAA G AG T G ATG GAACTG GTACTATCTATACAGAACTG GAACCACCTTGTAG GTTTGTTACAG AC
ACAC CTAAA G GTCCTAA
AG T G AAG TATTTATACTTTATTAAAG GATTAAACAACCTAAATAG AG G TATG G TACTTG G TAG
TTTAG CTG CCACAGTACG
TCTACAAG CTG G TAAT G CAAC AG AAG TG CCTG CCAATTCAACTGTATTATCTTTCTGTG CTTTTG
CTG TAG ATG CTG CTAAA
G CTTACAAAGATTATCTAG CTAGTG GG G G ACAACCAAT CACTAATTG TG TTAAG AT GTTGTG
TACACA CACTG GTACTG GT
CAG G CAATAACAGTTACACCG G AAG CCAATATG GATCAAGAATCCTTTG GTG GTG CATC
GTGTTGTCTGTACTG CC GTTG C
CAC ATAG ATCATC CAAATCCTAAAG GATTTTGTG ACTTAAAAG
GTAAGTATGTACAAATACCTACAACTTGTG CTAATG AC
CCTGTG G GTTTTACACTTAAAAACAC AG TCT G TAC C G TCTG C G GTATGTG G AAA G GTTATG
G CTG TAG TTG T G ATCAACTC
CG CGAACCCATG CTTCAGTCAG CTG ATG CACAATCGTTTTTAAACG GGTTTG CG
GTGTAAGTGCAGCCCGTCTTACACCGT
G CG G CA CAG G CACTAGTACTGATGTCGTATACAG G G CTTTTG ACATCTACAATGATAAAG TAG CTG
GTTTTG CTAAATTCC
TAAAAACTAATT G TT G TCG CTTCCAAG AAAAGG ACG AA GATG ACAATTTAATTG ATTCTT ACTTTG
TAG TT AAG AG ACACA
CTTTCTCTAACTACCAACATG AAG AAACAATTTATAATTTACTTAAG GATTGTCCAG
CTGTTGCTAAACATGACTTCTTTAA
GTTTAG AATAGACG G TG AC ATG G TACCACATATATCACGTCAACGTCTTACTAAATACACAATG G CAG
A CCTC G TCTATG C
TTTAAG G CATTTTG ATGAAG GTAATTGTGACACATTAAAAG
AAATACTTGTCACATACAATTGTTGTGATGATGATTATTTC
AATAAAAAG GACTG GTATG ATTTTG TAG AAAA CCCAG ATATATTAC G CG TATA CG CCAACTTAG
GTG AACGTGTACG CCA
AG CTTT G TTAAAAACA G TA C AATTCTG T G ATG CCATG CGAAATG CTG GTATTGTTG G TG
TACT G ACATTAG ATAAT CAAG A
TCTCAATG GTAACTG G TATG ATTTCG GTGATTTCATACAAACCACG CCAG GTAGTGG AG TTCCTG
TTGTAG ATTCTTATTAT
TCATTGTTAATG CCTATATTAACCTTGAC CAG G GCTTTAACTG CAG AG TC ACATG TTG A CACTG
ACTTAACAAA G CCTTACA
TTAAGTG G G ATTTG TTAAAATAT G A CTTCACG GAAG AG AG G TTAAAA CT CTTT G ACC G
TTATTTTAAATATTG G G AT CAG A
CATACCACCCAAATTGTGTTAACTGTTTG G AT G ACAG ATG CATTCTG CATTGTG
CAAACTTTAATGTTTTATTCTCTACAGT
GTTCCCACCTACAAGTTTTG G ACCACTAG TG AG AAAAATATTTGTTGATG GTG TTCCATTTG TAG
TTTCAACTG GATACCAC
TT CAG AG AG CTAG GTGTTGTACATAATCAG G ATGTAAACTTACATAG CT CTAG ACTTAGTTTTAAG G
AATTA CTTG TG TAT
G CTG CT G ACC CTG CTATG CACG CTG CTTCTG GTAATCTATTACTAGATAAACG CACTACGTG
CTTTTCAG TAG CTG C ACTTA
CTAACAATGTTG CTTTTCAAACTGTCAAACCCG GTAATTTTAACAAAG ACTTCTATG ACTTTGCTGTGTCTAAG
G G TTTCTTT
AAG GAAG GAAGTTCTGTTG AATTAAAACACTTCTTCTTTG CT CAG G ATG GTAATG CTG CTATC AG
CG ATTATGACTACTAT
CGTTATAATCTACCAACAATGTGTG
ATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACG
ATG GTG G CTGTATTAATG CTAACCAAG T CATCG TCAACAACCTAG AC AAATC AG CTG
GTTTTCCATTTAATAAATG G G G TA
AG G CTAG A CTTTATTATG ATTC AATG A G TTATG AG G AT CAAG ATG C A CTTTTCG C
ATATACAAAAC G TA ATG T CATCCCTAC
TATAACT CAAAT G AATCTTAA G TAT G CCATTAG TG C AAAG AATAG AG CTCG CACC G TAG
CTG GT G TCTCTAT CTG TA G TAC
TATG ACCAATAG ACAGTTTCATCAAAAATTATTG AAATCAATAG CCGCCACTAG AG G AG CTA CTG TAG
TAATTG GAACAA
G CAAATTCTATG GTG GTTG G CACAACATGTTAAAAACTGTTTATAGTG ATG TAG AAAACCCT
CACCTTATG G GTTG G GATT
ATCCTAAATGTG ATAG AG CCATG CC TAA CAT G CTTAG AATTATG G CCTCACTTG TT CTT G
CTCGCAAACATACAACGTGTTG
TAG CTTG TCA CAC CGTTTCTATAG ATTAG CTAATG AG TG TG CTCAAGTATTGAGTGAAATG GT
CATG TG TG G CG GTTC ACT
ATATGTTAAACCAG GTGGAACCTCATCAG G AG ATG CCACAACTG CTTATG
CTAATAGTGTTTTTAACATTTGTCAAGCTGT
CAC G GCCAATGTTAATG CACTTTTATCTACTGATG GTAACAAAATTG CC G ATAAGTATGTCCG
CAATTTACAACACAG ACTT
TAT G AG T GTCTCTATAG AAATAG AG ATGTTG AC ACAG ACTTTGTGAATG AGTTTTACG CATATTTG
CGTAAA CATTTCT CAA
TG ATGATACTCTCTG ACG AT G CT G TTG TG T G TTTCAATAG CACTTAT G CAT CTCAAG GT
CTAG T G G CTAG CATAAAG AACT
TTAA G TC AG TT CTTTATTAT CAAAAC AATG TTTTTAT G TCTG AAG CAAAATGTTG GACTG AG
ACTG AC CTTAC TAAAG GACC
TCATGAATTTTG CTCTCAACATACAATG CTAGTTAAACAGG G TG AT G ATTATG T G TAC CTTC
CTTACCCA G ATC CATCAAG A
ATCCTAG GG G CCG G CTGTTTTG TAG ATG ATATCG TAAAAACAGATG GTACACTTATGATTG AACG
GTTCG TGTCTTTAG CT
ATAGATG CTTA CC CACTTACT AAACAT CCTAATCAG GAG TATG
CTGATGTCTTTCATTTGTACTTACAATACATAAG AAAG C
TAC ATG AT G AG TTAAC AG G AC ACATG TTAG ACATG TATTCTG TTAT G CTTACTAAT G
ATAAC ACTT CAAG GTATTG G G AAC
CTG AGTTTTATG AG G CTATG TACACAC CG CATACAG TCTTAC AG G CTGTTG G G G CTTG TG
TT CTTTG CAATTCACAG ACTTC
ATTAAG AT G TG GTG CTTG CATACG TAG ACCATTCTTATGTTGTAAATG CTG TTACG A CCATG
TCATATCAAC ATCAC ATAAA
TTAGTCTTGTCTGTTAATCCGTATGTTTG CAATG CTCCAG GTTGTG ATGTCACAG ATG TG ACT
CAACTTTACTTAG GAG G TA
TG AG CTATTATTGTAAATCACATAAACCAC CCATTAGTTTTCCATTGTGTGCTAATG GACAAGTTTTTG
GTTTATATAAAAA
TACATGTGTTG G TAG CGATAATGTTACTGACTTTAATG CAATTG CAA CATG TG A CT G G AC AAATG
CTG GTGATTACATTTT
AG CTAACACCTG TACT G AAAG ACTCAAG CTTTTTG CAG CAGAAACG CTCAAAG CTA CTG AG G AG
A CATTTAAACTG TCTTA
TG GTATTG CTACTGTACGTG AA GT G CTG TCTG ACAG AG AATTACATCTTTCATG G G AAG TT G
GTAAACCTAGACCACCACT
TAACCGAAATTATGTCTTTACTG G TTATCG TG TAACTAAA AA CAGTAAAGTA CAAATAGG AG AGTA
CACCTTTG A AAAAG G
TG ACTATG GTGATG CTGTTGTTTAC CG AG GTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTG
CTG ACATCACAT
ACAGTAATG CCATTAAGTG CACCTACACTAGTG CCACAAG AG C ACTAT G TTAG AATTACTG G
CTTATACCCAACACTCAAT
ATCTCAG ATG AG TTTTCTAG CAATGTTG CAAATTATCAAAAG GTTG GTATG
CAAAAGTATTCTACACTCCAG G GACCACCT
G G TACT G G TAAG AG TCATTTTG CTATTG G CCTAG CTCTCTACTACCCTTCTG CTCG CATAG TG
TATA CAG CTTG CTCTCATG

CC G CTG TT G ATG CACTATG TG A G AAG G CATTAAAATATTTG CCTATAG ATAAATG TAG TA G
AATTATACCTG CA C G TG CTC
G T G TAG AG TG TTTTG ATAAATT CAAAG T G AATTCAA CATTAG AACA G TAT G TCTTTT G
TACTG TAAATG CATTG CCTG AGA
CG ACAG C AG ATATAG TTG T CTTT G ATG AAATTTCAATGG C CACAAATTAT G ATTTG A G TG
TTG TC AATG CCAG ATTACGTG
CTAAGCACTATGTGTACATTG G CGACCCTG CTCAATTACCTG CAC CACG CA CATTG CTAACTAAG G G
CA CA CTAG AAC CAG
AATATTTC AATTC AG TG TGTAG ACTTATG AAAACTATAG GTCCAG ACATGTTCCTCG G AACTTGTCG
G CGTTGTCCTG CTG
AAATTG TT G ACA CTG T G AG TG CTTTG GTTTATGATAATAAG CTTAAAG CAC ATAAAG
ACAAATCAG CT CAAT G CTTTAAAA
TGTTTTATAAG G GTGTTATCACG CATGATGTTTCATCTG CAATTAACAGG CCACAAATAG G
CGTGGTAAGAGAATTCCTTA
CAC GTAACCCTG CTTG G AG AAAAG CTG TCTTTATTTCAC CTTATAATTCACAG AATG CTG TAG
CCTCAAAG ATTTTG G GA CT
ACC AACT C AAACTG TTG ATTC ATC AC AG G G CTCAG AATAT G ACTATGT CATATTCACTC AAA
CCACTG AAAC AG CTC ACTCT
TGTAATG TAAAC AG ATTTAAT G TTG CTATTACCAG AG C AAAAG TAG G CATACTTTG CATAATG
TCTG ATAG A G ACCTTTAT
G AC AAG TTG CAATTTACAAG TCTT G AAATTCCAC G TAG GAATGTG G CAACTTTACAAG
CTGAAAATGTAACAG G ACT CTTT
AAAG ATTG TAG TAAG GTAATCACTG G GTTACATCCTACACAG G CAC CTACA C ACCT CAG TG TTG
ACACTAAATTCAAAACT
GAAG G TTTAT GTG TTG AC ATAC CTG G CATAC CTAAG GACATGACCTATAG
AAGACTCATCTCTATGATG G GTTTTAAAATG
AATTATCAAGTTAATG GTTACCCTAACATGTTTATCACCCG CGAAGAAG CTATAAGACATGTACGTG CATG
GATTG G CTTC
G ATGTC G AG G G GTGTCATG CTACTAG AG AAG CT GTTG GTACCAATTTACCTTTAC AG CTAG
GTTTTTCTACAG GTGTTAAC
CTAG TT G CTG TACCTACAG G TTATG TT G AT ACACCTAATAATACA G ATTTTT CCAG A G TTA
G TG CTAAACCACCG CCT G G A
G ATCAATTTAAACACCTCATACCACTTATGTACAAAG GACTTCCTTG G AATGTAGTG
CGTATAAAGATTGTACAAATGTTA
AGTG ACA CACTTAAAAAT CTCT CTG ACAG AG TCG TATTTGTCTTATG G G CA CATG
GCTTTGAGTTGACATCTATGAAGTATT
TTGTGAAAATAG G ACCTG AG CG CACCTGTTGTCTATGTG ATAG ACGTG CCACATG CTTTTCCACTG
CTTCAGACACTTATG
CCTGTTG G CATCATTCTATTG GATTTGATTACGTCTATAATCCGTTTATG ATTG ATGTTCAACAATG G GG
TTTTACAGGTAA
CCTACAAAG CAACCATGATCTGTATTGTCAAGTCCATG G TAATG CAC ATG T AG CTAG TTG TG AT G
C AAT CATG A CTAG GTG
TCTAG CTG TC CAC G AG TG CTTTGTTAAG C G TG TTG A CTG G ACTATTGAATATCCTATAATTG
GTGATG AACTG AAGATTAA
TG CG G CTTG TAG AAAG GTTCAACACATG GTTGTTAAAG CTG CATTATTAG CA G AC AAATTCCCAG
TTCTTCAC G A CATTG G
TAACCCTAAAG CTATTAAG TG TG TA CCTC AAG CT G ATG TAG AATG G AAG TT CTAT G ATG
CACAG CCTT G TAG TG ACAAAG C
TTATAAAATAGAAGAATTATTCTATTCTTATG CCACACATTCTGACAAATTCACAGATG GTGTATG CCTATTTTG
GAATTGC
AATGTCG ATAGATATCCTG CTAATTCC ATTGTTTG TAG ATTTG AC ACTAG AGTG
CTATCTAACCTTAACTTGCCTG GTTGTG
ATG GTG G CAGTTTGTATGTAAATAAACATG CATT CC ACACAC CAG CTTTTG ATAAAAGTG
CTTTTGTTAATTTAAAACAATT
ACCA _________ 1 1 1 1 1 CTATTACTCTG ACAGTCCATGTG AGTCTCATG GAAAACAAGTAGTGTCAG
ATATAGATTATGTACCACTAAAG
TCTG CTACGTGTATAACACGTTG CAATTTAG GTG GTG CTG T CTG T AG AC ATCATG CTAAT G AG
TACAG ATTG TATCTC G AT
G CTTATAACATGATG ATCTCAG CTG G CTTT AG CTTGTG G G TTTA CAAA CAATTT G ATA
CTTATAACCT CT G GAACACTTTTA
CAAG ACTT CAG A G TTT AG AAAATG T G GCTTTTAATGTTGTAAATAAG G G ACACTTTGATG G A
CAACAG G GT G AA G TACCA
GTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATG
GTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTG
TTAATG TAG CATTTG AG CTTTG G G CTAAGCG CAACATTAAACCAGTACCAG AG
GTGAAAATACTCAATAATTTG GGTGTG
G AC ATTG CTG CTAATACTGTGATCTG G G ACTAC AAAAG A G ATG CTCCAG
CACATATATCTACTATTG GTGTTTGTTCTATG
ACT G ACATAG CC AAG AAACCAACTG AAAC G ATTTG TG CAC CACT CACTG TCTTTTTTG AT G G
TAG A G TTG ATG G TCAAG TA
GACTTATTTAG AAATG CCCGTAATG GTG TTCTTATTACAGAAG GTAGTGTTAAAG GTTTACAACCATCTG
TAG GTCCCAAA
CAAG CTAGTCTTAATG GAGTCACATTAATTG GAG AAG CC GTAAAAACACAG TTCAATTATTATAAG AAAG
TTGATG GTG TT
GTCCAACAATTAC CTG AAA CTTA CTTTACTCAG AG TAG AAATTTACAAG AATTTAAACCCAG G AG TC
AAATG G AAATTG AT
TT CTTAG AATTAG CTATG GATG AATTCATTGAACG GTATAAATTAG AAG G CTATG
CCTTCGAACATATCGTTTATG G AG AT
TTTAGTCATAGTCAGTTAG GTG GTTTACATCTACTGATTGGACTAG CTAAACGTTTTAAG GAATCACCTTTTG
AATTAGAAG
ATTTTATTCCTATG G ACAG TA CAG TTAAAAACTATTTC ATAACAG AT G CG CAAACAG
GTTCATCTAAGTGTGTGTGTTCTGT
TATTG ATTTATTACTT G AT G ATTTTG TTG AAATAATAAAATCCCAAG ATTTATCT G TAG TTTCTAAG
G TT GTCAAAG TG ACT
ATTG ACTATACAG AAATTTCATTTATG CTTTG GTGTAAAGATGG C CATG TAG AA ACATTTTAC
CCAAAATTACAATCTA G TC
AAG CGTG G CAACCG GGTGTTG CTATG CCTAATCTTTACAAAATG CAAAGAATG CTATTAG AAAAG TG
TG AC CTTCA AAATT
ATG GTGATAGTG CAACATTACCTAAAG G CATAATG ATGAATGTCG CAAAATATACTCAA CT G TG
TCAATATTTAAACACAT
TAACATTAG CTG TACC CTATAATAT G AG AG TTATAC ATTTT G GTG CTG G TTCTG AT AAAG G
AG TT G CAC CAG G TA CAG CTG
TTTTAAGACAGTG GTTG CCTACG G GTACG CT G CTTGTCGATTCAG ATCTTAATG ACTTTGTCTCTG
ATG CAGATTCAACTTT
G ATTG G TG ATTG T G CAACTG TA CATAC AG CT AATAAATG G G ATCTC ATTATTAG T G
ATATG TAC G AC CCTAA G ACTAAAAA
TGTTACAAAAGAAAATG ACTCT AAAG AG G GTTTTTTCACTTACATTTGTG G GTTTATACAACAAAAG
CTAG CT CTTG G AG G
TTCCGTG G CTATAAAG ATA ACAG AA CATTCTTG GAATG CTG ATCTTTATAAG CT CATG GG AC
ACTTCGCATG GTG GACAG C
CTTTGTTACTAATGTGAATG CG TC AT CATCTG AAG CATTTTTAATTG GATGTAATTATCTTG G CAAA C
CA CGC G AA CA AATA
G AT G GTTATGTCATG CAT G CAAATTACATATTTTG G AG G AATACAAATCCAATT C AG TT G
TCTTC CTATTCTTTATTTG AC AT
G AG TAAATTTC CC CTTAAATTAAG G GGTACTG CTGTTATGTCTTTAAAAGAAG GTCAAATCAATGATATG
ATTTTATCTCTT
CTTAGTAAAG G TAG ACTTATAATTA G AG AAAACAAC AG AG TTG TTATTTCTA G TG
ATGTTCTTGTTAACAACTAAACGAAC
AATGTTTGTTTTTCTTGTTTTATTG CCA CTAGT CTCTAG TC AG TG TG TTAAT CTTAC AACCAG AACT
CAATTACCCCCTG CAT

ACACTAATTCTTTCACACGTG GTG TTTATTACCCTGACAAAGTTTTCAGATCCTCAGTTTTACATTCAACTCAG
GACTTGTTC
TTACCTTTCTTTTCCAATGTTACTTGGTTCCATG CTATAC AT GT CTCT G G G ACCAATG GT ACTAAG
AG GTTTG AT AAC CCTGT
CCTACCATTTAATGATG GTGTTTATTTTG CTTCCACTG AG AAG TCTAACATAATAAG AG G CTG G
ATTTTTG GTACTACTTTA
G ATTCG AAG ACC CAGTC CCTACTTATTGTTAATAAC G
CTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATG
ATCCATTTTTG G GTGTTTATTACCACAAAAACAACAAAAGTTGG ATG G AAAGTG AG TTCAG
AGTTTATTCTAGTG CG AATA
ATTG CACTTTTGAATATGTCTCTCAG CCTTTT CTTAT G G AC CTTG AAG G AAAACAG G
GTAATTTCAAAAATCTTAG G GAATT
TGTGTTTAAG AATATTGATG GTTATTTTAAAATATATTCTAAG CACACG C CTATTAATTTAGTG CGT G AT
CTCCCTCAG G GT
TTTTCG GCTTTAG AACCATTG GTAGATTTG CCAATAG GT ATTAACATC ACTAG GTTTCAAACTTTACTTG
CTTTA CATAG AA
GTTATTTG ACT CCTG GTG ATTCTTCTTCAGGTTG GACAG CTG GTG CTG CA G CTTATTATGTG G
GTTATCTTCAACCTAG G AC
TTTTCTATTAAAATATAATGAAAATG G AAC CATTAC AG ATG CTG TAG A CTGTG CACTTG AC CCTCT
CTCAG AAACAAAGTG
TACGTTG AAAT CCTT CACTG TAG AAAAAG G AAT CTATC AAACTTCTAA CTTTAG AG TCCAACCAA
CAG AATCTATTGTTAG A
TTTCCTAATATTACAAACTTGTG CCCTTTTG GTG AAGTTTTTAACG CCACCAGATTTG CATCTGTTTATG
CTTG G AACAG GA
AGAGAATCAG CAACTGTGTTG CTGATTATTCTGTCCTATATAATTCCG CATCATTTTCCACTTTTAAGTGTTATG
G AGTGT CT
CCTACTAAATTAAATGATCTCTG CTTTACTAATGTCTATG CAG ATTC ATTT GTAATTAG AG GT G ATG
AAGT CAG AC AAATCG
CT CCAG G GCAAACTG G AAA G ATT G CT G ATTATAATTATAAATTACCA G ATG ATTTTACAG G
CTG CGTTATAG CTTG G AATT
CTAACAATCTTG ATTCTAAG GTTG GTG GTAATTATAATTACCTGTATAGATTG TTTAG G
AAGTCTAATCTCAAACCTTTTGA
GAG AG ATATTTCAACTGAAAT CTATC AG GCCG GTAG CA CACCTTGTAATG GTGTTGAAG
GTTTTAATTGTTACTTTCCTTTA
CAATCATATG G TTTC CAACC CACTAATG G T GTTG G TTACCAACCATA CAG AG TAG TA
GTACTTTCTTTTG AACTTCTACATG
CAC CAG CAACTGTTTGTG G ACCTAAAAAGTCTACTAATTTG
GTTAAAAACAAATGTGTCAATTTCAACTTCAATG GTTTAAC
AG G CA CA G GTGTTCTTACTGAGTCTAACAAAAAGTTTCTG CCTTTCCAACAATTTG G CAG A GACATTG
CTGA C ACTACTGA
TG CTGTCCGTGATCCACAG ACACTTG AG ATTCTTG ACATTACACCATGTTCTTTTG GTG
GTGTCAGTGTTATAACACCAG GA
ACAAATACTTCTAACCAG GTTG CTGTTCTTTATCAG GATGTTAACTG C AC AGAAGTC CCTGTTG
CTATTCATG CAGATCAAC
TTACTCCTACTTG G CGTGTTTATTCTACAGGTTCTAATGTTTTTCAAACACGTG CAG G CTGTTTAATAG G G
G CTG AACATGT
CAA CAACT CATAT G AG TGTGACATACCCATTG GTG CA G GTATATG C G CTAGTTATCAG ACTC AG
ACTAATTCTCCTC G G CG
G G CACG TAGTG TAG CTAGTCAATCCATCATTG CCTACACTATGTCACTTG GTG
CAGAAAATTCAGTTGCTTACTCTAATAAC
TCTATTG CCATACCC A CAAATTTTAC TATTAGTG TTAC CACAG AAATT CTAC CAGT GTCTATG A
CCAAG A CATC AGTAG AU
GTACAATGTACATTTGTG G TGATTCAACTGAATG C AG CAATCTTTTGTTG CAATATG G CA
GTTTTTGTACAC AATTAAACCG
TG CTTTAACTG GAATAG CTGTTG AA CAAGAC AAAAACA CCCAAG AAGTTTTTG CA CAA GTCAAA
CAAATTTACAAAACACC
ACC AATTAAAGATTTTG GTG GTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAG CAAG A G G
TCATTTATT G AA
G AT CTAC TTTTC AAC AAAGTG ACACTTG CAGATG CTG GCTTC AT CAAACAATATG GT G
ATTGCCTTG GTGATATTG CTG CIA
G AG AC CTCATTT G TG CACAAAAGTTTAACG G CCTTACTGTTTTG CCACCTTTG CTCACAGATG
AAATG ATTG CTCAATACAC
TT CTG CACTGTTAG CG G GTACAATCACTTCTG GTTG G ACCTTTG GTG CAGGTGCTG
CATTACAAATACCATTTG CTATG CA
AATG GCTTATAG GTTTAATG GTATTG GAGTTACACAG AAT GTTCTCTATG AG AACCAAAAATTGATTG
CCAACCAATTTAA
TAG TG CTATT G G C AAAATT CAA GACTCACTTTCTT CCACAG CAAGTG CACTTG G AAAACTT
CAAG AT GTG GTCAACCAAAA
TG CACAAG CTTTAAACACG CTTGTTAAACAACTTAG CT C CAATTTTG GTG
CAATTTCAAGTGTTTTAAATG ATATC CTTT CAC
GT CTTG ACAAAGTTG AG G CTGAAGTG CAAATTGATAG GTTG ATCACAG G CAGACTTCAAAGTTTG CA
G ACATATGTG ACT
CAA CAATTAATTAG AG CTG CAGAAATCAG AG CTTCTG CTAATCTTG CTG CTACTAAAATG TCAG AG
TGTGTACTTG G ACAA
TCAAAAAGAGTTGATTTTTGTG GAAAG G G CTATCATCTTATGTCCTTCCCTCAGTCAG CACCTCATGG
TGTAGTCTTCTTG C
ATG TG A CTTAT GTC CCTG CACAAG AAAAG AACTTCACAACTG CTCCTG CCATTTGTCATGATG
GAAAAG CAC A CTTT CCT C
GTGAAG GTGTCTTTGTTTCAAATG G CAC ACA CTG GTTTGTAACACAAAG GAATTTTTATG
AACCACAAATCATTACTACAG
ACAACACATTTGTGTCTG GTAACTG TG AT GTT GTAATAG G AATTGTCAACAACACAGTTTATGATCCTTTG
CAACCTGAATT
AGA CTCATTCAAG GAG G AGTTAG ATAAATATTTTAAGAATCATACATCACCAG ATGTTGATTTAG GTG
ACATCTCTG G CAT
TAATG CTTCAGTTGTAAACATTCAAAAAG AAATTG AC CG CCTCAATG AG GTTG
CCAAGAATTTAAATGAATCTCTCATCGA
TCTCCAAG AACTTG GAAAGTATGAG CAGTATATAAAATG G CCATGGTACATTTGG CTAG GTTTTATAG
CTG G CTTGATTG C
CATAGTAATG GTG AC AATTATG CTTTG CTGTATG ACCAGTTG CTGTAGTTGTCTCAAG GG CTG TT
GTT CTTG TG G ATCCTG C
TG CAAATTTG ATG AAG ACGACTCTG AG CCAGTGCTCAAAG G AG TCAAATTACATTACAC ATAAACG
AACTTATG G ATTTGT
TTATG AG AATCTTCACAATTG G AA CTGTAACTTTG AAG CAAG GTG AAATCAAG GATG
CTACTCCTTCAGATTTTGTTCG CG
CTACTG CAACGATACCGATACAAG CCTCACTCCCTTTCG GATG G CTTATTGTTG G CGTTG CACTTCTTG
CTGTTTTTCAG AG
CG CTTCCAAAATCATAACCCTCAAAAAG AG ATG G CAA CTAG CACTCTCCAAG G GTGTTCACTTTGTTTG
CAACTTG CTG TT
GTTGTTTGTAACAG TTTA CTCAC A CCTTTTG CTCGTTG CTG CTG GCCTTG AAG
CCCCTTTTCTCTATCTTTATG CTTTAGTCTA
CTICTTGCAGAGTATAAACTITGTAAG AATAATAATG AG G CTTTG G CTTTG CTG GAAATG
CCGTTCCAAAAACCCATTACTT
TAT G ATG CCAACTATTTTCTTTG CTG G
CATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGT
CATTACTTCAG GT G ATG G C AC AACAAG TCCTATTT CTG AACATG ACTA CCAG ATTG GTG
GTTATACTG AAAAATG G GAATC
TG GAGTAAAAG ACT G TG TTGTATTAC ACAGTTACTTCACTTCA G ACTATTACCAG
CTGTACTCAACTCAATTG AGTACAG AC
ACT G GTGTTG AACATG TTA C CTTCTTCAT CTACAATAAAATTGTTG AT G AG C CTG AA GAACAT
GTC CAAATT CACACAATCG

ACGTTTCATCCGGAGTTGTTAATCCAGTAATGGAACCAATTTATG
ATGAACCGACGACGACTACTAGCGTGCCTTTGTAAG
CACAAGCTGATGAGTACGAACTTATGTACTCATTCGTTTCGG
AAGAGACAGGTACGTTAATAGTTAATAGCGTACTTCTTT
TTCTTGCTTTCGTGGTATTCTTGCTAGTTACACTAGCCATCCTTACTGCGCTTCGATTGTGTGCGTACTGCTGCAATAT
TGTT
AACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTC
TG GT
CTAAACGAACTAAATATTATATTAGTTTTTCTGTTTGGAACTTTAATTTTAGCCATGGCAGATTCCAACGGTACTATTA
CCGT
TGAAGAGCTTAAAAAGCTCCTTGAACAATGGAACCTAGTAATAGGTTTCCTATTCCTTACATGGATTTGTCTTCTACAA
TTT
GCCTATGCCAACAGGAATAG GTTTTTGTATATAATTAAGTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAG
CTTGTT
TTGTGCTTGCTGCTGTTTACAGAATAAATTGGATCACCGGTG GAATTGCTATCG
CAATGGCTTGTCTTGTAGGCTTGATGT
GGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGCGCGTACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACAT
TCT
TCTCAACGTG CCACTCCATG G CACTATTCTGACCAG ACC G CTTCTAG AAAGTGAACTCGTAATCG G AG
CTGTG ATCCTTCG
TG GACATCTTCGTATTG CTG G ACACCATCTAG GACG CTGTGACATCAAG GACCTG
CCTAAAGAAATCACTGTTGCTACATC
ACG AACG CTTTCTTATTACAAATTG G GAG CTTCG CAG CGTGTAG
CAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAG
GATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTGACAATATTGCTTTGCTTGTACAGTAAGTGACAACA
GA
TGTTTCATCTCGTTGACTTTCAG GTTACTATAGCAGAG ATATTACTAATTATTATG AG
GACTTTTAAAGTTTCCATTTGGAAT
CTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTCAATTAGATGAAG
AGC
AACCAATG GAG ATTG ATTAAACGAACATGAAAATTATTCTTTTCTTG G CACTGATAACACTCG CTACTTGTG
AG CTTTATCA
CTACCAAG AGTGTGTTAGAG GTACAACAG TACTTTTAAAAGAACCTTG CTCTTCTGGAACATACGAG
GGCAATTCACCATT
TCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCTGACGGCGTAAAA
CAC
GTCTATCAGTTACGTGCCAGATCAGTTTCACCTAAACTGTTCATCAG ACAAG AG
GAAGTTCAAGAACTTTACTCTCCAATTT
TTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTG
AACTTTCATTAATT
GACTTCTATTTGTG CTTTTTAG CCTTTCTG CTATTCCTTGTTTTAATTATGCTTATTATCTTTTG
GTTCTCACTTGAACTG CAA
GATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCAT
TTC
ACCAAG AATGTAGTTTACAGTC ATGTACTCAACATCAACCATATG TAG TTG
ATGACCCGTGTCCTATTCACTTCTATTCTAA
ATG GTATATTAG AGTAG GAG CTAGAAAATCAGCACCTTTAATTGAATTGTGCGTGGATGAGG
CTGGTTCTAAATCACCCA
TTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGG
AACCTAAATTGGGTAGTCTT
GTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACA
AAC
TAAAATGTCTGATAATGGACCCCAAAATCAG
CGAAATGCACCCCGCATTACGTTTGGTGGACCCTCAGATTCAACTGGCA
GTAACCAGAATGGAGAACGCAGTG GG GCGCGATCAAAACAACGTCG
GCCCCAAGGTTTACCCAATAATACTGCGTCTTG
GTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCG
AGGACAAGGCGTTCCAATTAACACCAATAGCAG
TCCAGAT GACCAAATTG G CTACTACCGAAG AG CTACCAGACGAATTCGTG GTG GTG ACG
GTAAAATGAAAG ATCTCAGTC
CAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATG
G
GTTG CAACTG AG G G AG CCTTGAATACACCAAAAGATCACATTG G CACCCG CAATCCTG
CTAACAATGCTGCAATCGTG CT
ACAACTTCCTCAAG GAACAACATTG CCAAAAG G CTTCTACGCAGAAG G GAG CAGAG G CGG
CAGTCAAGCCTCTTCTCGTT
CCTCATCACGTAGTCG CAACAGTTCAAGAAATTCAACTCCAGGCAG CAG TAG G G GAACTTCTCCTGCTAG
AAT G G CTG GC
AATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCC
A
ACAACAACAAG GCCAAACTGTCACTAAGAAATCTGCTGCTGAGG
CTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTA
AAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAAT
C
AGACAAGG AACTGATTACAAACATTG GCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAG
CGTTCTTCGGAATGTCGCGC
ATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATT
T
CAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAA
A
AGAAGAAG GCTGATGAAACTCAAG CCTTACCG CAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGCTG
CAGAT
TTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGACCACA
CA
AGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTA
ACT
ACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTAATCAGTGTGTAACATTAG G GAG
GACTTG AAA
GAG CCACCACATTTTCACCGAG GCCACGCGGAGTACGATCG
AGTGTACAGTGAACAATGCTAGGGAGAGCTGCCTATAT
G GAAG AG CCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGCTTCTTAGGAGAAT
SEQ ID NO: 10 >Severe acute respiratory syndrome coronavirus 2 orf1ab polyprotein of isolate hCoV-19/Italy/INM11-is1/2020 (Genbank Acc. No: 0IA98553) M ESLVPGFNE KTHVQLSLPVLQVRDVLVRG FGDSVEEVLSEARQHLKDGTCG
LVEVEKGVLPQLEQPYVFIKRSDARTAPHG H
VMVE LVAELE G 1 QYG RSG ETLGVLVP HVG El PVAYR KVL LR K NG N KGAGG HSYGADLKSF
DLG DELGTDPYE DFQENWNTKH
SSGVTRELM RE LNGGAYTRYVDNN FCG P DGYPLECIKDLLARAGKASCTLSEQLDF
IDTKRGVYCCREHEHEIAWYTERSEKSYE
LQTPFEIKLAKKFDTFNGECPNFVFPLNSIIKTIQPRVEKKKLDGFMGRIRSVYPVASPNECNQMCLSTLMKCDHCGET
SWQTG
DFVKATCEFCGTENLTKEGATTCGYLPQNAVVKIYCPACHNSEVGPEHSLAEYHNESGLKTILRKGGRTIAFGGCVFSY
VGCHNK

CAYWVPRASAN IGCNHTGVVGEGSEG LN D N LLEI LQKEKVN IN IVG DFKLNEEIAI I
LASFSASTSAFVETVKGLDYKAF KQIVESC
G N F KVTKGKAKKG AWN IG EQKSI LSPLYAFASEAARVVRSI FSRTLETAQNSVRVLQKAAITI
LDGISQYSLRLIDAM MFTSDLAT
NN LVVMAYITGGVVQLTSQWLTN I FGTVYE KLKPVLDWL EE KF KEG VEF LR
DGWEIVKFISTCACEIVGG QIVTCAKE I KESVQT
F FKLVNKFLALCADSI I IGGAKLKALN LG ETFVTHS KG LYRKCVKSREETGLLM P LKAPKE I I F
LEG ETLPTEVLTEEVVLKTG DLQP L
EQPTSEAVEAPLVGTPVCI NGLM LLE I KDTEKYCALAPNM MVTN NTFTLKGGAPTKVTFG DDTVI
EVQGYKSVN ITF E LDERI DK
VLNEKCSAYTVELGTEVNEFACVVADAVIKTLQPVSELLTPLG I DLDEWSMATYY LF DESG EF KLASH
MYCSFYP P DED EEEG DC
E E EEF E PSTQYEYGTEDDYQGKP LE FGATSAALQPE
EEQEEDWLDDDSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEM ELTP
VVQTI EVNSFSGYLKLTDNVYIKNADIVEEAKKVK PTVVVNAAN VYLKHGGGVAGALN KATN NAM QVESD
DYIAT NG P LKVG
GSCVLSGHNLAKHCLHVVG PNVNKG EDIQLLKSAYENF NQH EVLLAPLLSAG I FGADPI HS
LRVCVDTVRTNVYLAVF DKN LYD
KLVSSFLEM KSEKQVEQKIAEI PK EEVKP FITESKPSVEQRKQDDKKIKACVEEVTTTLEETKFLTENLLLYI
DI NG NLH PDSATLVSD
I DITF LK KDAPYIVG DVVQEGVLTAVVI PTKKAGGTTEM LAKALRKVPTDNYITTYPGQG LNG
YTVEEAKTVLKKCKSAFYILPSI IS
NEKQEI LGTVSWN LREMLAHAEETRKLM
PVCVETKAIVSTIQRKYKGIKIQEGVVDYGARFYFYTSKTTVASLINTLN DLN ETLVT
M PLGYVTHG LN LE EAA RYM RSLKVPATVSVSSPDAVTAYNGYLTSSSKTPE EH F I
ETISLAGSYKDWSYSG QSTQLG I E FLKRG D
KSVYYTSNPTTFHLDGEVITFDNLKTLLSLREVRTIKVFTTVDN IN LHTQVVDMSMTYGQQFG PTYLDGADVTKI
KPH NSH EG KT
FYVLPNDDTLRVEAFEYYHTTDPSF LGRYMSALN HTKKWKYPQVNGLTSIKWADNNCYLATALLTLQQI
ELKFNPPALQDAYYR
ARAGEAAN FCALILAYCNKTVGE
LGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQFKKGV
QIPCTCGKQATKYLVQQESPFVM MSAPPAQY ELKHGTFTCASEYTG NYQCG HY KH ITSKETLYCI
DGALLTKSSEYKGPITDVFY
KENSYTTTI KPVTYKLDGVVCTEI DP KLD NYYKKDNSYFTEQPI DLVP NQPYPNASF DN F KFVCD NI
KFADDLNQLTGYKKPASRE
LKVTFF PDLNGDVVAI DYKHYTPSF KKGAKLLH
KPIVWHVNNATNKATYKPNTWCIRCLWSTKPVETSNSFDVLKSEDAQGM D
N LACEDLKPVSE EVVEN PTIQKDVLECNVKTTEVVG D I I LKPA NNS LKITE EVG
HTDLMAAYVDNSSLTI KKPN E LSRVLG LKTLAT
HGLAAVNSVPWDTIANYAKPFLNKVVSTTTNIVTRCLNRVCTNYM PYFFTLLLQLCTFTRSTNSRIKASM
PTTIAKNTVKSVGKF
CLEASF NYLKSP N FSKLI NI I IWF LLLSVCLGSLIYSTAALGVLMSN LGM
PSYCTGYREGYLNSTNVTIATYCTGSIPCSVCLSG LDSL
DTYPSLETIQITISSFKWDLTAFGLVAEWFLAYILFTRFFYVLGLAAIMQLFFSYFAVH F ISNSWLMWLI I
NLVQMAPISAM VR MY
IF FASFYYVWKSYVHVVDGCNSSTCM MCYKR NRATRVECTTIVNGVR RSFYVYANGG KG FCKLH
NWNCVNCDTFCAGSTF IS

NVI VFDG KSKCE ES
SAKSASVYYSQLMCQP I LLLDQA LVSDVG DSAEVAVK M FDAYVNTFSSTFNVPME
KLKTLVATAEAELAKNVSLDNVLSTF ISAA
RQGFVDSDVETKDVVECLKLSHQSDI EVTGDSCNNYMLTYN KVENMTP RDLGACI DCSAR H I NAQVAKSH
NIALIWNVKDF M

LITPVHV MSKHTDFSSE II
GYKAI DGGVTR DIASTDTCFAN K HADFDTW FSQRGGSYTNDKACP LIAAVITREVG FVVPG
LPGTILRTTNGD F LH FLPRVFSAV
GNICYTPSKLI EYTDFATSACVLAAECTIF KDASGKPVPYCYDTNVLEGSVAYESLRPDTRYVLM DGSI I QF
P NTYLEGSVRVVTTF
DSEYCRHGTCERSEAGVCVSTSG RWVLN NDYYRSLPGVFCG VDAVN LLTN M FTPLIQP
IGALDISASIVAGGIVAIVVTCLAYYF
M RF RRAFG EYSHVVAF NTLLF LMSFTVLCLTPVYSF LPGVYSVIYLYLTFYLTNDVSF LAH I QW M VM
FTPLVPFWITIAYIICISTK
HFYWF FSNYLKRRVVFNGVSFSTFEEAALCTFLLNKEMYLKLRSDVLLP
LTQYNRYLALYNKYKYFSGAMDTTSYREAACCH LAK
ALNDFSNSGSDVLYQPPQTSITSAVLQSGFRKMAF PSG KVEGCMVQVTCGTTTLNG LWLDDVVYCP RHVICTSE
DM LNP NYE
DLLIRKSN HNFLVQAGNVQLRVIGHSMQNCVLKLKVDTANPKTP KYKFVRIQPGQTFSVLACYNGSPSGVYQCAM
RP NFTI KG
SF LNGSCGSVG F NI DYDCVSFCYM H H M ELPTGVHAGTDLEGNFYG PFVDRQTAQAAGTDTTITVN
VLAW LYAAVI NG DRWF
LNRFTTTLNDFN LVAMKYNYE PLTQDHVDILG PLSAQTGIAVLDMCASLKELLQNGMNG
RTILGSALLEDEFTPF DVVRQCSGV
TFQSAVK RTI KGTH HW LL LTI LTSLLVLVQSTQWSLF F FXYENAF LPFAMG I IAMSAFAM M
FVKHKHAFLCLFLLPSLATVAYF N
MVYMPASWVM RI MTWLDMVDTSLSGF KLKDCVMYASAVVLLILMTARTVYDDGARRVWTLM NVLTLVYKVYYG
NALDQA
ISMWALIISVTSNYSGVVTTVM F LARG IVF M CVEYCP I F FITG
NTLQCIMLVYCFLGYFCTCYFGLFCLLN RYFRLTLGVYDYLVST
QEF RYM NSQG LLPPKNSI DAF KLN I KLLGVGGKPCI
KVATVQSKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHN DI LLA
KDTTEAFE KM VSLLSVLLSM QGAVDI N KLCEEMLDN RATLQAIASEFSSLPSYAAFATAQEAYEQAVANG
DSEVVLKKLKKSL N
VAKSE F DRDAAM QRKLEKMADQAMTQMYKQARSED KRAKVTSAM QTM LFTM LRK LDN DALN NI I N
NAR DGCVPLN I IP LT
TAAKLMVVI PDYNTYKNTCDGTTFTYASALWEIQQVVDADSKIVQLSEISM
DNSPNLAWPLIVTALRANSAVKLQNN ELSPVAL
RQMSCAAGTTQTACTDDNALAYYNTTKGG RFVLALLSDLQDLKWARFPKSDGTGTIYTELEPPCRFVTDTPKGP
KVKYLYFI KG
LNNLNRG MVLGSLAATVRLQAG NATEVPANSTVLSFCAFAVDAAKAYKDYLASGGQPITNCVKM
LCTHTGTGQAITVTPEAN
M DQESFGGASCCLYCRCH IDH PNP KGFCDLKG KYVQI PT-I-CAN DPVG FTLKNTVCTVCG
MWKGYGCSCDQLR EP M LQSADA
QSFLNRVCGVSAARLTPCGTGTSTDVVYRAFDIYNDKVAGFAKFLKINCCRFQEKDEDDN LI DSYFVVKR
HTFSNYQHE ETIYN L
LKDCPAVAKH DFFKF RI DG DMVPH ISRQRLTKYTM ADLVYALRH F DEG NCDTLKEI
LVTYNCCDDDYFNKKDWYDFVENPDIL
RVYANLG ERVRQALLKTVQFCDAM RNAG IVGVLTLD NQDLNG N WY DFG DF
IQTTPGSGVPVVDSYYSLLM PI LTLTRALTA ES
HVDTDLTK PYI KWDLLKYDFTEER LK LFDRYF KYW DQTYH PNCVNC LDDRCI LHCAN FNVLFSTVFP
PTSFG P LVRK I FVDGVP F

NVAFQTVKPGNF N KDFYD FA
VSKG FFKEGSSVELKHFFFAQDG NAAISDYDYYRYNLPTMCDIRQLLFVVEVVDKYFDCYDGGCINANQVIVN
NLDKSAGFPFN
KWGKARLYYDSMSYEDQDALFAYTKRNVIPTITQMN LKYAISAKNRARTVAGVSICSTMTNRQF
HQKLLKSIAATRGATVVIGT
SKFYGGWH NM LKTVYSDVE N PH L MGWDYPKCDRAM P NML RI M ASLVLARKHTTCCSLSHR FYR
LAN ECAQVLSEMVMCG

GSLYVKPGGTSSGDATTAYANSVF NICQAVTANVNALLSTDGN KIADKYVRN LQH
RLYECLYRNRDVDTDFVNEFYAYLRKH FS
M MILSDDAVVCFNSTYASQGLVASIKN FKSVLYYQNNVFMSEAKCWTETDLTKGPH EFCSQHTM LVKQG
DDYVYLPYPDPSRI
LGAGCFVDDIVKTDGTLM I E RFVSLAI DAYPLTKH P NQEYADVF H LYLQYI RKLH DE LTG
HMLDMYSVM LTNDNTSRYWEPEF
YEAMYTPHTVLQAVGACVLCNSQTSLRCGACIRRPFLCCKCCYDHVISTSHKLVLSVNPYVCNAPGCDVTDVTQLYLGG
MSYYC
KSHKPPISFPLCANGQVFGLYKNTCVGSDNVIDFNAIATCDVVINAGDYI
LANTCTERLKLFAAETLKATEETFKLSYGIATVREVL
SDRE LH LSWEVG K P RP PL NRNYVFTGYRVTKNSKVQIG EYTF EKG DYG
DAVVYRGTTTYKLNVGDYFVLTSHTVM PLSAPTLVP
QEHYVRITGLYPTLNISDEFSSNVANYQKVGMQKYSTLQG PPGTG
KSHFAIGLALYYPSARIVYTACSHAAVDALCEKALKYLPID
KCSRIIPARARVECF D KFKVNSTLEQYVFCTVNAL PETTADIVVF DE ISMATNYDLSVVNAR LRAKHYVYIG
DPAQLPAPRTLLTK
GTLEPEYFNSVCRLM KTIG P DM F LGTCRRCPAEIVDTVSALVYDN KLKAHKDKSAQCFKM
FYKGVITHDVSSAIN RPQIGVVREF
LTRNPAWRKAVFISPYNSQNAVASKI LGLPTQTVDSSQGSEYDYVIFTQTTETAHSCNVNRFNVAITRAKVGILCI
MSDRDLYDK
LQFTSLEIPRRNVATLQAENVTG LFKDCSKVITGLHPTQAPTHLSVDTKFKTEG LCVDIPGIPKDMTYRRLISMMG
F KM NYQVN
GYPNM FITREEAIRHVRAWIG F DVEGCHATREAVGTNLP LQLG FSTGVN LVAVPTGYVDTP N
NTDFSRVSAKP PPG DQFKH LI
PLMYKGLPWNVVRIKIVQM LSDTLKNLSDRVVFVLWAHG FELTSM
KYFVKIGPERTCCLCDRRATCFSTASDTYACWHHSIGF
DYVYNPF MIDVQQWG FTG NLQSNHDLYCQVHGNAHVASCDAI MTRCLAVHECFVKRVDWTI EYPI I G DE
LKI NAACR KVQH
MVVKAALLADKFPVLH DIGNPKAIKCVPQADVEWKFYDAQPCSDKAYKI
EELFYSYATHSDKFTDGVCLFWNCNVDRYPANSI
VCRFDTRVLSNLNLPGCDGGSLYVNKHAFHTPAFDKSAFVN LKQLPFFYYSDSPCESHG
KQVVSDIDYVPLKSATCITRCNLGGA
VCRH HAN EYRLYLDAYN M M ISAG FSLWVYKQF DTYN LW NTFTRLQSLE NVAF NVVN KG H
FDGQQG EVPVSI I N NTVYTKVD
GVDVELF E NKTTLPVNVAF E LWAK RN IKPVPEVKI LN
NLGVDIAANTVIWDYKRDAPAHISTIGVCSMTDIAKKPTETICAP LTVF
FDGRVDGQVDLFRNARNGVLITEGSVKGLQPSVGPKQASLNGVTLIG
EAVKTQFNYYKKVDGVVQQLPETYFTQSRNLQEFKP
RSQM E I DF LELA M DEFI ERYKLEGYAFEHIVYGDFSHSQLGG LH LL IG LAKRF KESPF E LE DF
I PM DSTVKNYFITDAQTGSSKCVC
SVI DLLLD DFVE II KSQDLSVVSKVVKVTIDYTEISFM LWCKDG HVETFYPKLCISSQAWQPGVAMPN
LYKMQRMLLE KC DLQN
YG DSATLPKG I M M NVAKYTQLCQYLNTLTLAVPYNM RVI
HFGAGSDKGVAPGTAVLRQWLPTGTLLVDSDLN DFVSDADSTL I
G DCATVHTAN KW DLIISDMYDPKTKNVTKENDSKEGFFTYICG FIQQKLALGGSVAIKITEHSWNADLYKLMGH
FAWWTAFV
TNVNASSSEAF LIGCNYLG KP REQIDGYVM HANYI FWRNTN PIQLSSYSLFDMSKFPLKLRGTAVMSLKE
SEQ ID NO: 11 >Protein \S_2019-nCoV/Ita ly-IN M I 1 (Sprotein_hCoV19Ita lyIN MI1is12020)(G
en ba nk Acc. No: QIA98554) M FVF LVLLP LVSSQCVN LTTRTQLP PAYTNSFTRGVYYPDKVF RSSVLHSTQDLF LP FFSNVTWF HAI
HVSGTNGTK RF DN PVLP
F N DGVYFAST EKSN II RGW IFGTTLDSKTQSLLIVN NATNVVI KVCEFQFCN DP FLGVYY1-11(N N
KSW M ESEF RVYSSAN NCTF EY
VSQPF LM DLEGKQG NFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGIN
ITRFQTLLALHRSYLTPGDSSSG
WTAGAAAYYVGYLQPRTFLLKYNE
NGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRVQPTESIVRFPNITNLCPFGEVFN
ATRFASVYAWN RKRISNCVADYSVLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRG
DEVRQIAPGQTGKIADYNYKLPDD
FTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQP
YRVVV
LSFELLHAPATVCG PKKSTNLVKNKCVN FN F NG LTGTGVLTESN KKF
LPFQQFGRDIADTTDAVRDPQTLEILDITPCSFGGVSVI
TPGTNTSNQVAVLYQDVNCTEVPVAI HADQLTPTVVRVYSTGSNVFQTRAGCLIGAE
HVNNSYECDIPIGAGICASYQTQTNSP
RRARSVASQS1lAYTMSLGAENSVAYSN NSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICG
DSTECSNLLLQYGSFCTQLNRALT
G IAVEQD KNTQEVFAQVKQIYKTP PI KDFGG F NFSQILP DPSKPSKRSFI E DL LF N KVTLADAG
FIKQYG DCLGDIAARDLICAQKF
NG LTVLPPL LTDE M IAQYTSALLAGTITSG WTFGAGAALQI P FAM QMAYRFNG IGVTQNVLYE
NQKLIANQF NSAIG KIQDSLS
STASALG KLQDVVNQNAQALNTLVKQLSSN FGAISSVLNDILSRLDKVEAEVQIDRLITG RLQSLQTYVTQQLI
RAAEI RASAN LA
ATKMSECVLGQSKRVDFCG KGYHLMSFPQSAPHGVVF LHVTYVPAQEKNFTTAPAICHDG KAH FP
REGVFVSNGTHWFVTQ
RNFYEPQIITTDNTFVSG NCDVVIG IVNNTVYDPLOPELDSFKEELDKYFKNHTSPDVDLG DISG I
NASVVNIQK El DRLN EVAKN
LN ESLI DLQELG KYEQYI KWPWYIW LG F IAG LIAIVM VTI M
LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
SEQ ID NO: 12 >hCoV-19/France/IDF0372-is1/20201EPI ISL 41072012020-01-23 ATTAAAGGTTTATACCTTCCCAGGTAACAAACCAACCAACTTTCGATCTCTTGTAGATCTGTTCTCTAAACGAACTTTA
AAA
TCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGA
CA
CGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTCG
TCC
GGGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGT
T
TTACAGGTTCGCG ACGTG CTCG TACGTG G CTTTG GAGACTCCGTGGAG GAG GTCTTATCAGAG
GCACGTCAACATCTTAA
AGATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGT
TC
GGATGCTCGAACTGCACCTCATGGTCATGTTATGGTTGAGCTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGT
G
GTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACGG
TA
ATAAAGGAGCTGGTGGCCATAGTTACGGCGCCGATCTAAAGTCATTTGACTTAGGCGACGAGCTTGGCACTGATCCTTA
T
GAAGATTTTCAAGAAAACTGGAACACTAAACATAG CAG TGGTGTTACCCGTGAACTCATG CGTGAGCTTAACGG
AG GG G

CATACACTCG CTATGTCGATAACAACTTCTGTG G CC CTG AT G G CTACCCTCTTGAGTG CATTAAAG
ACCTTCTAG CACGTG C
TG GTAAAG CTTCATG CACTTTGTCCG AACAACTG GACTTTATTG ACACTAAG AG G G GTGTATACTG
CTG CCGTG AACATG A
G CATGAAATTG CTTG GTACACG G AACGTTCTGAAAAG AG CT ATG AATTG CAG A CACCTTTT G
AAATTAAATTG G CAAAGA
AATTTG A CAC CTTCAATG G G
GAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAG G GTTG A
AAAG AAAAAG CTTG ATG GCTTTATG G GTAGAATTCG AT CTGTCTATCCAGTTG CGTCACCAAATG
AATG CAACCAAATGT
G CCTTTCAACTCTCATGAAGTGTG ATCATTGTG GTG AAACTTCATG G CAGACG G G CGATTTTGTTAAAG
CCACTTG CG AAT
TTTGTG G CAC TG AG AATTTG ACTAAAG AAG GTGCCACTACTTGTG GTTACTTACCCCAAAATG CTG
TTGTTAAAATTTATTG
TCCAG CATGTCACAATTCAG AA GTA GG AC CTG AG CATAGTCTTG CCGAATACCATAATG AATCTG G
CTTGAAAACCATTCT
TCGTAAG GGTG GTC G CACTATTG CCTTTGG AG GCTGTGTGTTCTCTTATGTTG G TTG
CCATAACAAGTGTG CCTATTG G GT
TCCACGTG CTAG CGCTAACATAGGTTGTAACCATACAG GTGTTGTTG GAG AAG GTTCCG AAG G
TCTTAATG ACAACCTT CT
TG AAATACTC CAA AAAGA G AAAG TCAAC ATCAATATTG TT G GTG ACTTTAAACTTAATG AAG AG
ATC G CCATTATTTTG GC
ATCTTTTTCTG CTTCCACAAGTG CTTTTGTG G AAA CTGTG AAA G GTTTG G ATTATAAAG
CATTCAAACAAATTGTTG AATCC
TGTG GTAATTTTAAAGTTACAAAAG GAAAAG CTAAAAAAG GTG CCTG
GAATATTGGTGAACAGAAATCAATACTG AGTCC
TCTTTATG CATTTG CATC AG AG G CTG CTCGTGTTGTACG ATCAATTTTCTCC CG CA CT CTTG
AAACTG CTCAAAATTCTGTG C
GTGTTTTACAG AAGG CCG CTATAACAATACTAGATG G AATTT CACAG TATT CACTG AG ACT CATTG
ATG CTATGATGTTCA
CAT CTG ATTTG G CTACTAA CAATC TAG TTGTAATG G CCTACATTACAG GTG GTGTTGTTCAGTTG A
CTTC G CAG TG G CTAA
CTAACATCTTTG GCACTGTTTATG AAAAACTCAAACCCGTCCTTGATTG G CTTG AA G AG AAGTTTAAG G
AAG GTGTAGAGT
TT CTTAGAG ACG GTG G GAAATTGTTAAATTTATCTCAACCTGTG CTTGTG AAATTGTCG GTG
GACAAATTGTCACCTGTG
CAAAGGAAATTAAG GAG A GTGTTCAG ACATTCTTTAAG CTTGTAAATAAATTTTTGG CTTTGTGTG CTG
ACTCTATCATTAT
TG GTG GAG CTAAACTTAAAG CCTTGAATTTAG GTG AAACATTTGTCACG CACTCAAAG G G
ATTGTACAG AAAGTGTG TTA
AATCCAG AG AA G AAACTGG CCTACTCATG CCTCTAAAAGCC CCAAAAG AAATTATCTTCTTAG AG GG
AG AAA CACTTCC CA
CAG AAGT GTTAACAG A G GAAGTTGTCTTG AAAACTG GTG ATTTA CAA CC ATTAG
AACAACCTACTAGTGAAG CTGTTG AA
G CTCCATTG GTTG G TA CAC CAGTTTGTATTAAC G G G CTTATGTTG CTC G AAATC AAAG AC
ACAG AAAAGTACTGTG CCCTT
G CACCTAATATG ATG GTAACAAACAATACCTTCACACTCAAAG G CG GTG CACCAACAAAG GTTACTTTTG
GTG ATG ACA CT
GTGATAGAAGTG CAAG GTTACAAG AGTGTGAATATCACTTTTGAACTTGATG AAAG G ATTG
ATAAAGTACTTAATG AG AA
GTG CTCTG CCTATACAGTTG AACTCG GTACAGAAGTAAATGAGTTCG CCTGTGTTGTG G CAG AT G
CTGTCATAAAAACTTT
G CAACCAGTATCTGAATTACTTACACCACTG G G CATTG ATTTAGATGAGTG G AG TATG G
CTACATACTACTTATTTGATGA
GT CT G GTGAGTTTAAATTG G CTTCA CATAT GTATTG TTCTTTCTACCCT CCAG ATG AG GATG AAG
AAGAAG GTG ATTG TG A
AGAAG AAG AGTTTG AG CCATCAACTCAATATG AGTATG GTACTG AAGATGATTACCAAG
GTAAACCTTTGG AATTTG GTG
CCACTTCTG CTG CTCTTCAACCTGAAGAAG AG CAAG AAGAAGATTG GTTAGATGATG
ATAGTCAACAAACTGTTG GT CAA
CAAG ACG G CAGT G AG G AC AAT CAG A CAACTACTATTCAAA CAATT GTTG AG
GTTCAACCTCAATTAG AG AT G G AA CTTA C
ACC AGTT GTTC AG ACTATTG AAGTG AATAGTTTTAGTGGTTATTTAAAACTTACTG
ACAATGTATACATTAAAAATG CAG A
CATTGTG GAAG AAG CTAAAAAG GTAAAACCAACAGTG GTTGTTAATG CAG CCAATGTTTACCTTAAACATG
GAG G AGG T
GTTG C AG G AG CCTTAAATAAG G CTACTAACAATG CCATG CAAGTTGAATCTGATGATTACATAG
CTACTAATG G ACC ACTT
AAAGTG G GTG G TAG TTGTGTTTTAAG CG G ACACAATCTTG CTAAACACTGTCTTCATGTTGTCG G C
CCAAATGTTAAC AAA
G GTG AA G ACATTCAACTTCTTAAG AGTG CTTAT G AAAATTTTAAT C AG CAC GAAGTTCTACTTG
CACC ATTATTATC AG CTG
GTATTTTTG GT G CT G AC CCTATAC ATTCTTTAAG AG TTTG TGTAG ATACTGTT CG CA CAAATG
TCTA CTTAG CTGTCTTTG AT
AAAAATCTCTATG A CAAACTTGTTTCAAG CTTTTTG GAAATG AAG AG T G AAAAG CAA G TTG
AACAAAAGATCG CTG AG AT
TCCTAAAG AG G AAGTTAAG C C ATTTATAACTGAAA GTAAA CCTT CAGTTG AAC AG AG AAAACAAG
ATG ATAAG AAAAT CA
AAG CTTG TGTTG AAG AAG TTACAACAACT CT G G AAG AAACTAAG TTCCT CAC AGAAAACTT
GTTACTTT ATATT G ACATTA
ATG G CAATCTTCATCCAGATTCTG CCACT CTTG TTAG T G AC ATTG AC ATCA CTTT CTTAAAG
AAA G ATG CTCCATATATAGT
G G GTG ATG TTGTT CAAG AG G GTGTTTTAACTG CTGTG GTTATACCTACTAAAAAG G CTG GTG G
CACTACTG AAATG CTAG
CG AAAG CTTTG AG AAAAGTG CCAAC AG ACAATTAT ATAAC CACTTACCC G G GTCAG G
GTTTAAATG GTTACACTGTAG AG
GAG G CAAAGACAGTG CTTAAAAAGTGTAAAAGTG CCTTTTACATTCTACCATCTATTATCT CTAATG AG
AAG CAAG AAATT
CTTG G AA CTGTTTCTTG G AATTTG CG AG AAATG CTTG CACATG CAG AAG AAACACG
CAAATTAATGC CTGTCTGTGTG GA
AACTAAAGCCATAGTTTCAACTATACAG CGTAAATATAAG G GTATTAAAATACAAG AG G
GTGTGGTTGATTATG GTG CIA
G ATTTTACTTTTACACCAGTAAAACAACTG TAG
CGTCACTTATCAACACACTTAACGATCTAAATGAAACTCTTGTTACAAT
G CCACTTG G CTATGTAACACATG G CTTAAATTTG G AAG AA G CTG CT CG GTATATG AG AT CT
CT CAAAGTG CCAG CTACAGT
TT CTGTTTCTTCAC CTG ATG CT G TTACAG CGTATAATG G TTATCTTACTTCTTCTT CTAAAA CAC
CTG AAG AACATTTTATTG
AAACCATCTCACTTG CT G GTTCCTATAAAG ATTG GTCCTATTCTG GACAATCTACACAACTAG GTATAG
AATTT CTTAAG AG
A G G TG ATAAAA G TGTATATTA CA CTA G TAAT CCTAC CACATT CCA CCTA G ATG
GTGAAGTTATCACCITTG A C AATCTTAA G
ACACTTCTTTCTTTGAG AG AAGTG AG GACTATTAAG GTGTTTACAACAG TAG
ACAACATTAACCTCCACACG CAA GTTG TG
GACATGTCAATG ACATATG G ACAACAGTTTG GTCCAACTTATTTG GATG GAG CTG
ATGTTACTAAAATAAAACCTCATAAT
TCACATG AAG GTAAAACATTTTATGTTTTACCTAATG AT GACACTCTA CG TG TTG AG G
CTTTTGAGTACTACCACACAACTG
ATCCTAGTTTTCTG G GTAG GTACATGTCAG CATTAAATCACACTAAAAAGTG GAAATACCCACAAGTTAATG
GTTTAACTT

CTATTAAATG G G CAGATAACAACTGTTATCTTG CCACTG CATTGTTAACACTC CAACAAATAG AG TTG
AAGTTTAAT C CA CC
TG CT CTACAAG AT G CTTATTACAG AG CAAG G G CTG G TG AA G CTG CTAACTTTTGTG CA
CTTATCTTAG CCTACTGTAATAA
G AC AG TAG GTG AG TTAG GTGATGTTAG AG AAAC AAT G A G TTA CTTGTTTCAACATG
CCAATTTAG ATTCTTG CAAAAG AG
TCTTG AACGTG GTGTGTAAAACTTGTG GACAACAG CAGACAACCCTTAAG G GTG TAG AAG
CTGTTATGTACATG G G CACA
CTTTCTTATG AACAATTTAAG AAA G G TG TT CAG ATACCTTG TAC G TG TG G TAAAC AA G
CTACAAAATATCTAGTACAACAG
G AG TCAC CTTTTG TTATG ATGTCAG CA CCACCTG CT CAG TATG AA CTTAAG CAT G
GTACATTTACTTGTG CTAG TG AG TACA
CT G GTAATTACCAGTGTG GTCACTATAAACATATAACTTCTAAAG AAACTTTG TATTG C ATA G AC G
GTG CTTTACTTACAAA
G T CCTC A G AATAC AAAG GTCCTATTACG G AT G TTTT CTA CAAAG AAAACAG TTACA CAACAA
CCATAAAACCA G TTA CTTA
TAAATTG GATG G TG TTGTTTG TACAG AAATT G AC CCTAAG TTG GACAATTATTATAAG AAAG
ACAATT CTTATTTC A CAG A
G CAACCAATTGATCTTGTACCAAACCAACCATATCCAAACG CAAG CTTCG
ATAATTTTAAGTTTGTATGTGATAATATCAAA
TTTG CT G ATG ATTTAAACCAGTTAACTGGTTATAAG AAACCTG CTTCAA G AG AG
CTTAAAGTTACATTTTTCCCTG ACTTAA
ATG GTG ATGTG GTG G CT ATTG ATTATAAACACTACACACCCTCTTTTAAG AAAG GAG
CTAAATTGTTACATAAACCTATTG
TTTGG CATGTTAACAATG CAACTAATAAAG CCACGTATAAACCAAATACCTG GTGTATACGTTGTCTTTG G
AG CAC AAAAC
CAGTTG AAACAT CAAATT C G TTTG ATG TA CTG AA G TCAG AG G AC G C G CAG G GAATG
GATAATCTTG CCTGC GAAGATCTA
AAACCAGTCTCTG AAG AAG TAGTG G AAAATCCTACCATACAGAAAG ACGTTCTTG AG TGTAATGTG
AAAACTACCG AAGT
TG TAG G AG ACATTATACTTAAACCAG CAAATAATAGTTTAAAAATTACAG AAG AG GTTG G CCACACAG
ATCTAATG G CTG
CTTATG TAG A C AATTCTAGT CTTACTATTAAG AAACCTAATG AATTATCTAG AG TATTAG GTTTG
AAAACCCTTG CTACTCA
TG GTTTAG CTG CTGTTAATAGTGTCCCTTG G G ATACTATAG CTAATTATG CTAAG
CCTTTTCTTAACAAAGTTGTTAGTACA
ACTACTAACATAG TTACACG GTGTTTAAACCGTGTTTGTACTAATTATATG CCTTATTTCTTTACTTTATTG
CTACAATTGTG
TACTTTTACTAG AAGTACAAATTCTAGAATTAAAG CATCTATG CC G ACTACTATAG
CAAAGAATACTGTTAAG AG TG TC G G
TAAATTTTG TCTAG A G G CTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTG
ATAAATATTATAATTTG GTTTTTACT
ATTAAGTGTTTG CCTAG G TTCTTTAAT CTACTCAA CC G CTG CTTTAG GTGTTTTAATGTCTAATTTAG
G CATG CCTTCTTACT
GTACTG G TTACAG AG AA G G CTATTTGAACTCTACTAATGTCACTATTG CAA CCTACTG TACTG
GTTCTATACCTTG TAG TG T
TT G TCTTAG TG GTTTAG ATTCTTTAG ACACCTATCCTTCTTTAGAAACTATACAAATTAC
CATTTCATCTTTTAAATG G GATTT
AACTGCTTTTG G CTTAGTTG CAGAGTG GTTTTTG G CATATATTCTTTTCACTAG GTTTTTCTATGTACTTG
GATTG G CTG CAA
TCATG CA ATTG TTTTTCAG CTATTTTG CAGTACATTTTATTAGTAATTCTTG G CTTATGTG
GTTAATAATTAATCTTGTACAA
ATG G CCCCGATTTCAG CTATG GTTAGAATGTACATCTTCTTTG CATCATTTTATTATGTATG
GAAAAGTTATGTGCATGTTG
TAG ACG G TTG TAATT C ATC AACTT G TAT G ATG TG TTACAAA C G TA ATA G AG CAAC
AAG AG T C G AATG TAC AACTATTG TTA
ATG GTGTTAG AAG GTCCTTTTATGTCTATG CTAATG G AG GTAAAG G CTTTTG CAAACTACACAATTG
G AATTGTGTTAATT
GTGATACATTCTGTG CTG G TAG TACATTTATTAG TG ATG AAGTTG CGAG AG ACTTGTCACTACAG
TTTAAAAG AC CAATAA
ATCCTACTGACCAGTCTTCTTACATCGTTGATAGTGTTACAGTG AAGAATG G TTCCATC CAT CTTTACTTT G
ATAAAGCTG G
TCAAAAGACTTATGAAAG ACATTCTCTCTCTCATTTTGTTAACTTAG ACAACCTG A G AG
CTAATAACACTAAAG GTTCATTG
CCTATTAATGTTATAGTTTTTG ATG GTAAATCAAAATGTG AAGAATCATCTGCAAAATCAG
CGTCTGTTTACTACAGTCAG C
TTATG T G TCAA CCTATACTG TTACTAG AT CAG G CATTAGTGTCTG ATG TT G GTGATAGTG CG G
AAGTTG CAGTTAAAATGT
TT G ATG CTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATG GAAAAACTCAAAACACTAGTTG
CAACTG CAG AAG C
TG AACTTG CAAA G AATG TG T CCTTAG AC AAT G TCTTAT CTACTTTTATTT CA G CA G CTCGG
CAAG G GTTTGTTG ATTCA G AT
G TAG AAA CTAAA G ATG TTG TTG AATG T CTTA AATTG TCA CATCAATCT G AC ATA G AAG
TTA CTG G C G ATAG TT G TAATAAC
TATATG CTCACCTATAACAAAGTTGAAAACATG ACACCCCGTG ACCTTG GT G CTTGTATTGACTGTAGTG
CG CGTCATATT
AATG CG C AG G T AG CAAAAAGTCACAACATTG CTTTGATATG G AA C G TTAAA G ATTTCAT G
TCATTG T CTG AACAACTAC G A
AAAC AAATAC G TAG TG CT G CTAAAAAGAATAACTTACCTTTTAAGTTGACATGTG CAACTACTA G
ACAA G TT G TTAATG TT
GTAACAACAAAGATAG CACTTAAGG GTG GTAAAATTGTTAATAATTG G TTG AA G
CAGTTAATTAAAGTTACACTTGTGTTC
CTTTTTGTTG CTG CTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTG A CTTTTCAAG TG
AAATCATAG G
ATACAAG G CTATTGATGGTG GTGTCA CTCG TG AC ATAG
CATCTACAGATACTTGTTTTGCTAACAAACATGCTGATTTTG A
CAC ATG GTTTAG CCAG CGTG GTG GTAGTTATACTAATGACAAAG CTTG CCCATTGATTG CTG CAG
TCATAACAAG AG AAG
TG G GTTTTGTCGTG CCTG G TTTG CCTG G CAC GATATTACG CACAACTAATG GTGACTTTTTG
CATTTCTTACCTAG AG TTTT
TAG TG CA GTTG GTAA CATCTGTTA CACACCATCAAAACTTATAG AG TACAC TG ACTTTG
CAACATCAG CTTGTGTTTTG G CT
G CTG AAT GTACAATTTTTAAAG AT G CTTCTGGTAAG CCAG TACCATATT G TTATG ATACCAATG TA
CTAG AAG GTTCTGTTG
CTTATG AAAGTTTACG CCCTG ACACACGTTATGTG CTCATG G ATG G
CTCTATTATTCAATTTCCTAACACCTACCTTG AAG G
TT CTG TTAG A G TG GTAACAACTTTTG ATTCT G AG TA CTG TAG G CAC G G CACTTG TG AAA
G ATC AG AAG CTG GTGTTTGTGT
ATCTACTAGTG G TA G ATG G GTACTTAACAATGATTATTACAGATCTTTACCAG G AG TTTTCTG TG G
TG TAG AT G CTG TAAA
TTTACTTA CTAATATEITTA CAC CA CTAATTC AACCTATTG G TG CTTTG GACATATCAG
CATCTATAGTAGCTGGTG GTATT
G TAG CTATC G TAG TAACAT GCCTTG CCTACTATTTTATG AG GTTTAG AAG A G CTTTTG GTG
AATACA G TCATG TAG TT G CCT
TTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTG
GTGTTTATTCTGTTAT
TTACTTG TACTTG AC ATTTTATCTTACT AATG AT G TTTCTTTTTTAG CAC ATATTCAGTG GATG
GTTATGTTCACACCTTTAGT
ACCTTTCTG GATAACAATTG CTTATATCATTTGTATTTCCACAAAG CATTTCTATTG G TTCTTTAG
TAATTACCTAAAG AG AC

G T G TAG TCTTTAATG GTGTTTCCTTTAGTACTTTTGAAGAAG CT G CG CTGTG CACCTTTTTG
TTAAATAAAGAAAT G TAT CT
AAAGTTG CG TAG TG ATGTG CTATTACCTCTTACG CAATATAATAG ATACTTAG
CTCTTTATAATAAGTACAAGTATTTTAGT
G GAG CAATG GATACAACTAG CTACAG A G AAG CTG CTTG TT G TCATCTCG CAAAG G CTCTCAAT
G ACTT CAG TAACTC AG G
TT CTG ATG TTCTTTACCAACCACCACAAA CCT CTATCA CCTCA G CTGTTTTG CA G AG T G
GTTTTAGAAAAATG G CATTCCCA
TCTG GTAAAGTTG AG G GTTGTATG GTACAAGTAACTTGTG GTACAACTACACTTAACG GTCTTTG G
CTTG ATG AC G TAG TT
TACTGTCCAAG AC ATG TGATCTG CACCTCTG AAG AC ATG CTTAACCCTAATTATGAAG
ATTTACTCATTCGTAAGTCTAATC
ATAATTTCTTG GTACAG G CT G GTAATGTTCAACTCAG G GTTATTG GACATTCTATG CAAAATTG TG
TA CTTAA G CTTAAG G
TT G ATAC AG CC AATCCTAAG A CACCTAAG TATAAGTTTG TTCG CATTCAACCAG G AC
AGACTTTTTCA G TG TTAG CTTGTTA
CAATGGTTCACCATCTG GTGTTTACCAATGTG CTAT GAG G CCCAATTTCACTATTAAGG G TT CATTC
CTTAATG GTTCATGT
G GTAGTGTTG GTTTTAACATAG ATTATGACTGTGTCTCTTTTTGTTACATG CACCATATG G AATTAC CAA
CTG G AG TTCATG
CTG G CAC AG ACTTAG AA G GTAACTTTTATG G ACCTTTTGTTG ACAG G CAAAC AG C AC AAG
CAG CTG GTACG GACACAACT
ATTACAG TTAATGTTTTAGCTTG G TTGTACGCTGCTGTTATAAATG G AG ACAG GTGGTTTCTCAATCG
ATTTACCACAACTC
TTAATG ACTTTAACCTTGTG G CTATG AAGTACAATTATG AACCTCTAACACAAG ACCAT G TT G
ACATACTA G G AC CT CTTTC
TG CT CAA ACTG G AATTGCCGTTTTAGATATGTGTG CTTCATTAAAAGAATTACTG CAAAATG
GTATGAATGG ACGTACCAT
AUG G GTAGTG CTTTATTAG AA GATG AATTTACACCTTTTG ATG TTG TTAG ACAATG CTCAG
GTGTTACTTTCCAAAGTG CA
GTGAAAAG AACAATCAAG G GTACACACCACTG G TTG TTACT CACAATTTT G ACTT CACTTTTAG
TTTTAG TCCAG AG TACTC
AATG GT CTTT G TTCTTTTTTTTG TATG AAAATG CCTTTTTACCTTTTG CTATG G GTATTATTG
CTATGTCTGCTTTTG CAAT G A
TGTTTGTCAAACATAAG CAT G CATTTCTCTGTTTGTTTTTGTTACCTTCTCTTG CC A CTG TA G
CTTATTTTAATATG GT CTATA
TG CCTG CTAG TTG G GTGATG C GTATTATG AC ATG GTTG GATATG GTTG ATACTAGTTTGTCTG
GTTTTAAGCTAAAAG ACT
GTGTTATGTATG CAT CAG CTGTAGTGTTACTAATCCTTATG ACAG CAAGAACTGTGTATG ATGATG GTG
CTAG G AG AGTG
TG GACACTTATGAATGTCTTGACACTCGTTTATAAAGTTTATTATG GTAATG CTTTAG AT CAAG
CCATTTCCATGTG G G CTC
TTATAATCTCTG TTACTTCTAACTA CTC AG G TG TAG TTACAACTG T CATG TTTTTG G CCAG A G
GTATTGTTTTTATG TG TG TT
G AG TATT G CC CTATTTTCTTCATAACTG GTAATACACTTCAGTGTATAATGCTAGTTTATTGTTTCTTAG G
CTATTTTTG TACT
TGTTACTTTGG CCTCTTTTGTTTACTCAACC G CTACTTTAG ACTG A CTCTTG GTGTTTATG
ATTACTTAGTTTCTACACAG GA
GTTTAG ATATATG AATTCAC AG GG ACTA CTCCCA CCCAAG AATAG CATAGATG
CCTTCAAACTCAACATTAAATTGTTG GG
TGTTG GTGG CAAAC CTTG TATC AAA GTAG CC A CT G TA CAG T CTAAAATG T CAG ATG
TAAAG TG C ACAT CAG TA G TCTTACT
CTC A G TTTTG CAACAACTCAG AG TA G AATC ATCAT CTAAATTGT G G G
CTCAATGTGTCCAGTTACACAATG ACATTCTCTTA
G CTAAAG ATACTACTG AAG CCTTTG AAAAAATG GTTTCACTACTTTCTGTTTTG CTTTCCATG CAGG
GTG CTGTAGACATAA
ACAAGCTTTGTGAAG AAATG CTG G ACAAC AG G G CAA CCTTAC AAG CTATAG CCTC A G AG
TTTAG TTC CCTT CCATC ATATG
CAG CTTTTG CTACTG CTCAAG AAG CTTATG AG CAG G CTGTTG CTAATG GTG ATTCTG AAG TTG
TTCTTAAAAAG TTG AAG A
AGTCTTTGAATGTG G CTAAATCTG AATTTG AC CGTG ATG CAG CCATG CAACGTAAGTTG GAAAAGATG
G CTGATCAAG CT
ATG ACCCAAATGTATAAACAG G CTAGATCTG AG G A CAAG AG G G CAAAAGTTACTAGTG CTATG
CAG ACAATG CTTTTCAC
TAT G CTTAG AAAG TT G GATAATGATG CA CTCAA C AAC ATTATC AACAAT G CAAG A G AT G
GTTGTGTTCCCTTGAACATAAT
ACCTCTTACAACAG CAG CCAAACTAATG G TTG TCATA CCAG A CTATAACAC ATATAAAAATACG TG
TG ATG G TAC AA CATT
TACTTATG CAT CAG CATTGTG G G AAATCCAACAG G TT G TAG AT G C AG ATAGTAAAATTG
TTCAA CTTAG TG AAATTAGTAT
G GACAATTCACCTAATTTAG CATG G CCTCTTATTGTAACAG CTTTAAG GG CCAATTCTG CTG
TCAAATTACA GAATAATG A
G CTTAGTCCTGTTG CACTACGACAGATGTCTTGTG CTG CCG GTACTACACAAACTGCTTG CACTG ATG A
CAATG CGTTAG C
TTACTACAACACAACAAAG GG AG GTAG GTTTG TACTTG CACTGTTATCCGATTTACAG GATTTG AAATG
G G CTAGATTCCC
TAA G AG T G ATG G AACTG GTACTATCTATACAG AACTG G AAC C AC CTT GTAG GTTTGTTACAG
AC ACAC CTAAA G GTCCTAA
AG T G AAG TATTTATA CTTTATTAAAG GATTAAACAACCTAAATAG AG G TAT G G TA CTTG G TAG
TTTA G CTG CCACAGTACG
TCTACAAG CTG G TAAT G CAAC AG AAG TG CCTG CCAATTCAACTGTATTATCTTTCTGTG CTTTTG
CTG TAG ATG CTG CTAAA
G CTTACAAAGATTATCTAG CTAGTG GG G G ACAACCAAT CACTAATTG TG TTAAG AT GTTGTG
TACACA CACTG GTACTG GT
CAG G CAATAACAGTTACACCG GAAG CCAATATG G ATCAAGAATCCTTTG GTG GTG CATC
GTGTTGTCTGTACTG CCGTTG C
CAC ATAG ATCATC CAAATCCTAAAG GATTTTGTG ACTTAAAAG
GTAAGTATGTACAAATACCTACAACTTGTG CTAATG AC
CCTGTG G GTTTTACACTTAAAAACACAGTCTGTACC GTCTG CG G TAT G TG GAAAG GTTATG G CTG
TAG TTG TG ATCAACTC
CG CGAACCCATG CTTCAGTCAG CTG ATG CAC AATCG TTTTTAAAC G GGTTTG CG
GTGTAAGTGCAGCCCG TCTTACACC GT
G CG G CA CAG G CACTAGTACTGATGTCGTATACAG G G CTTTTG ACATCTACAATGATAAAG TAG CTG
GTTTTG CTAAATTCC
TAAAAACTAATTG TTGTCG CTTCCAAG AAAAGG ACG AAG ATGACAATTTAATTG ATTCTT ACTTTG
TAGTTAAG AG ACACA
CTTTCTCTAACTACCAACATG AAG AAACAATTTATAATTTACTTAAG GATTGTCCAG CTG TT G
CTAAACATG ACTT CTTTAA
GTTTAG AATAGACG G TG AC ATG G TACCACATATATCACGTCAACGTCTTACTAAATACACAATG G CAG
A CCTC G TCTATG C
TTTAAG G CATTTTG ATGAAG GTAATTGTG A CACATTAAAA G AA ATA CTTGTCAC ATACAATTG TTG
TG ATGATG ATTATTTC
AATAAAAAG GACTG GTATG ATTTTG TAG AAAA CCCAG ATATATTAC G CG TATA CG CCAACTTAG
GTG AACGTGTACG CCA
AG CTTT G TTAAAAACA G TA C AATTCTG T G ATG CCATG CGAAATG CTG GTATTGTTG G TG
TACT G ACATTAG ATAAT CAAG A
TCTCAATG GTAACTG G TATG ATTTCG GTGATTTCATACAAACCACG CCAG G TAG TGG AGTTC CTG
TTGTAG ATTCTTATTAT
TCATTGTTAATG CCTATATTAACCTTGAC CAG G GCTTTAACTG CAG AG TC ACATG TTG A CACTG
ACTTAACAAA G CCTTACA

TTAAGTG GG ATTTGTTAAAATATGACTTCACG G AAG AG AG G
TTAAAACTCTTTGACCGTTATTTTAAATATTG GG AT CAG A
CATACCACCCAAATTGTGTTAACTGTTTG G AT G ACAG ATG CATTCTG CATTGTG
CAAACTTTAATGTTTTATTCTCTACAGT
GTTCCCACCTACAAGTTTTG G ACCACTAG TG AG AAAAATATTTGTTGATG GTG TTCCATTTG TAG
TTTCAACTG GATACCAC
TT CAG AG AG CTAG GTGTTGTACATAATCAG G ATGTAAACTTACATAG CT CTAG ACTTAGTTTTAAG G
AATTA CTTG TG TAT
G CTG CT G ACC CTG CTATG CACG CTG CTTCTG GTAATCTATTACTAGATAAACG CACTACGTG
CTTTT CAG TAG CTG CACTTA
CTAACAATGTTG CTTTTCAAACTGTCAAACCCG GTAATTTTAACAAAG ACTTCTATG ACTTTGCTGTGTCTAAG
G G TTTCTTT
AAG GAAG GAAGTTCTGTTG AATTAAAACACTTCTTCTTTG CT CAG G ATG GTAATG CTG CTATCAG
CGATTATG ACTACTAT
CGTTATAATCTACCAACAATGTGTG
ATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACG
ATG GTG G CTGTATTAATG CTAACCAAG T CATCG TCAACAACCTAG AC AAATC AG CTG
GTTTTCCATTTAATAAATG G G G TA
AG G CTAG A CTTTATTATG ATTCAATG AG TTAT G AG GATCAAG ATG CACTTTTCG
CATATACAAAACGTAATGTCATCCCTAC
TATAACT CAAAT G AATCTTAA G TAT G CCATTAG TG C AAAG AATAG AG CTCG CACC G TAG
CTG GT G TCTCTAT CTG TA G TAC
TATG ACC AATAG ACAGTTTCATCAAAAATTATTGAAATCAATAG CCGCCACTAG AG GAG
CTACTGTAGTAATTG GAACAA
G CAAATTCTATG GTG GTG G CA CAACATGTT AAAAACTG TTTATAGTG ATG TAG
AAAACCCTCACCTTATGG GTTG G GATT
ATCCTAAATGTG ATAG AG CCATG CC TAA CAT G CTTAG AATTATG G CCTCACTTG TT CTT G
CTCGCAAACATACAACGTGTTG
TAG CTTG TCACACCGTTTCTATAG ATTAG CTAATG AG TG TG CTCAAG TATTG AG TG AAATG
GTCATGTGTGG CG GTTC ACT
ATATGTTAAACCAG GTGGAACCTCATCAG G AG ATG CCACAACTG CTTATG
CTAATAGTGTTTTTAACATTTGTCAAGCTGT
CAC G GCCAATGTTAATG CACTTTTATCTACTGATG GTAACAAAATTG CC G ATAAGTATGTCCG
CAATTTACAACACAG ACTT
TAT G AG TGTCTCTATAG AAATAG A G ATG TTG ACACAG ACTTTGTGAATG AGTTTTACG CATATTTG
CGTAAACATTTCTCAA
TG ATGATACTCTCTGACG ATG CTG TT G TG TG TTTCAATAG CA CTTATG CATCTCAAG GTCTAGTG
G CT AG CATAAAGAACT
TTAA G TC AG TT CTTTATTAT CAAAAC AATG TTTTTAT G TCTG AAG CAAAATGTTG GACTG AG
ACTG AC CTTAC TAAAG G ACC
TCATGAATTTTG CT CTCAA CATAC AATG CTAG TTAAAC AG G G TG ATG ATTATG TG TACCTTC
CTTACCC AG ATC CATC AAG A
ATCCTAG GG G CCG G CTGTTTTG TAG ATG ATATCG TAAAAACAGATG GTACACTTATGATTG AACG
GTTCG TGTCTTTAG CT
ATAG ATG CTTACCCACTTACTAAACATCCTAATCAG G AG TATG CTG AT G TCTTTC ATTT
GTACTTACAATACATAAG AAAG C
TAC ATG ATG AG TTAA CAG G ACACATG TTAG AC ATG TATTCTG TTATG
CTTACTAATGATAACACTTCAAG GTATTG G GAAC
CTG AGTTTTATG AG G CTATG TACACAC CG CATACAG TCTTAC AG G CTGTTG G G G CTTG TG
TT CTTTG CAATTCACAG ACTTC
ATTAAG ATGTGGTG CTTG CATACG TAG ACCATT CTTATG TT G TAAATG CT G TTACG AC CATG T
CATAT CAACAT CACATAAA
TTAGTCTTGTCTGTTAATCCGTATGTTTG CAATG CTCCAG GTTGTG ATGTCACAG ATG TG ACT
CAACTTTACTTAG GAG G TA
TG AG CTATTATTGTAAATCACATAAACCAC CCATTAGTTTTCCATTGTGTGCTAATG GACAAGTTTTTG
GTTTATATAAAAA
TACATGTGTTG G TA G CGATAATGTTACTG ACTTTAATG CAATTG CAAC ATG T G A CT G
GACAAATG CTG GTGATTACATTTT
AG CTAACACCTG TACT G AAAG ACTCAAG CTTTTTG CAG CAGAAACG CTCAAAG CTA CTG AG G AG
A CATTTAAACTG TCTTA
TG GTATTG CTACTGTACGTG AA GT G CTG TCTG ACAG AG AATTACATCTTTCATG G G AAG TT G
GTAAACCTAGACCACCACT
TAACCGAAATTATGTCTTTACTG G TTATC G TG TAACTAAAAACAG TAAAG TA CAAATAG G AG AG
TACACCTTTG AAAAAG G
TG ACTATG GTGATG CTGTTGTTTAC CG AG GTACAACAACTTACAAATTAAATGTTGGTGATTATTTTGTG
CTG ACATCACAT
ACAGTAATG CCATTAAGTG CA CCTA C ACTAG TG C CACAAG AG CA CTATG TTAG AATTACTG G
CTTATACCCAACACTCAAT
ATCTCAG ATG AG TTTTCTAG CAATGTTG CAAATTATCAAAAG GTTG GTATG
CAAAAGTATTCTACACTCCAG G GACCACCT
G G TACT G G TAAG AG TCATTTTG CTATTG G CCTAG CTCTCTACTACCCTTCTG CTCG CATAG TG
TATA CAG CTTG CTCTCATG
CCG CTGTTGATG CACTATGTG A G AAG GCATTAAAATATTTG CCTATAG ATAAATG TAG TAG
AATTATACCTG CA C G TG CTC
G T G TAG AG TG TTTT G ATAAATTC AAAG TG AATT CAACATTAG AA CAG TATG TCTTTT G
TACT G TAAATG CATTG CCTG AGA
CG ACAG C AG ATATAG TTG T CTTT G ATG AAATTTCAATGG C CACAAATTAT G ATTTG A G TG
TTG TC AATG CCAG ATTACGTG
CTAAGCACTATGTGTACATTG G CG ACCCTG CTCAATTACCTG CACCACG CACATTG CTAACTAAG G G
CACACTAG AACCAG
AATATTTC AATTC AG TG TGTAG ACTTATG AAAACTATAG GTCCAG ACATGTTCCTCG G AACTTGTCG
G CGTTGTCCTG CTG
AAATTG TT G ACA CTG T G AG TG CTTTG GTTTATGATAATAAG CTTAAAG CAC ATAAAG
ACAAATCAG CT CAAT G CTTTAAAA
TGTTTTATAAG G GTGTTATCACG CATGATGTTTCATCTG CAATTAACAGG CCACAAATAG G CGTG
GTAAGAGAATTCCTTA
CAC GTAACCCTG CTTG G AG AAAAG CTG TCTTTATTTCAC CTTATAATTCACAG AATG CTG TAG
CCTCAAAG ATTTTG G GA CT
ACCAACTCAAACTGTTGATTCATCACAG G G CT CAG AATATG ACTAT GTC ATATT CACTC AAACCACTG
AAACAG CTC A CTCT
TGTAATG TAAACAGATTTAATGTTG CTATTACCAG AG CAAAAG TAG G CATACTTT G CATAATG T CTG
ATAG A G ACCTTTAT
G AC AAG TTG CAATTTACAAG TCTT G AAATTCCAC G TAG GAATGTG G CAACTTTACAAG
CTGAAAATGTAACAG G ACT CTTT
AAAG ATTG TAG TAAG GTAATCACTG G GTTACATCCTACACAG G CAC CTACAC ACCTC AG TG TTG
A CACTAAATTCAAAACT
GAAG G TTTATG TG TTG AC ATAC CTG GCATACCTAAG G ACATGACCTATAG AAG ACT
CATCTCTATG ATG G GTTTTAAAATG
AATTATCAAGTTAATG GTTACCCTAACATGTTTATCACCCG CGAAGAAG CTATAAGACATGTACGTG CATG
GATTG G CTTC
G ATGTC G AG G G GTGTCATG CTACTAG AG AAG CTGTTGG TACCAATTTAC CTTTACAGCTAG G
TTTTTCTA CA G G TG TT AA C
CTAG TT G CTG TACCTACAG G TTATG TT G AT ACACCTAATAATACA G ATTTTT CCAG A G TTA
G TG CTAAACCACCG CCT G G A
G AT CAATTTAAA CACCT CATACCACTTATG TACAAAGG ACTTCCTTG G AATGTAGTG
CGTATAAAGATTGTACAAATGTTA
AG T G ACA CACTTAAAAAT CTCT CTG ACAG AG TCG TATTTGTCTTATG G G CA CATG GCTTTG
AG TT G ACAT CTAT G AAG TATT
TTGTGAAAATAG G ACCTG AG CG CACCTGTTGTCTATGTG ATAG ACGTG CCACATG CTTTTCCACTG
CTTCAGACACTTATG

CCTGTTG G CATCATTCTATTG GATTTGATTACGTCTATAATCCGTTTATGATTG ATGTTCAACAATG G
GGTTTTACAGGTAA
CCTACAAAG CAAC CATG ATCT G TATTG T CAAG T C CAT G G TAATG C ACAT GTAG CTAG TT
G TG ATG C AAT CATG ACTAG GTG
TCTAG CTG TC CAC G AG TG CTTTGTTAAG C G TG TTG A CTG G ACTATTGAATATCCTATAATTG
GTGATG AACTG AAGATTAA
TG CG G CTTG TAG AAAG GTTCAACACATG GTTGTTAAAG CT G CATTATTAG CA G ACAAATTC C
CA G TTCTTCA C G A CATTG G
TAACCCTAAAG CTATTAAGTGTGTACCTCAAG CTG ATG TA G AATG GAAG TTCTATG AT G CAC AG C
CTTG TAG TG ACAAAG C
TTATAAAATAGAAGAATTATTCTATTCTTATG CCACACATTCTGACAAATTCACAGATG GTGTATG CCTATTTTG
GAATTGC
AATGTCG ATAGATATC CTG CTAATT C C ATT GTTTG TA G ATTTG AC ACTAG AGTG
CTATCTAACCTTAACTTG CCTG GTTGTG
ATG GTG G CAGTTTGTATGTAAATAAACATG CATT CC ACACAC CAG CTTTTG ATAAAAGTG
CTTTTGTTAATTTAAAACAATT
AC C ATTTTT CTATTACT CTG ACA G TC CAT G TG AG T CT CATG G AAAA C AAG TAG TG
TCAG ATATAGATTATGTACCACTAAAG
TCTG CTACGTGTATAACACGTTG CAATTTAGGTG GTG CT G TCTG TA G ACAT CATG CTAAT G AG
TACAG ATTG TATCT C G AT
G CTTATAACATGATG ATCTCAG CTG G CTTT AG CTTGTG G G TTTA CAAA CAATTT G ATA
CTTATAAC CT CT G GAACACTTTTA
CAA G ACTT CAG A G TTT AG AAAATG T G GCTTTTAATGTTGTAAATAAG G G ACACTTTGATG G
ACAACAG G GT G AA G TAC C A
GTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATG GTGTTG ATG TAG AATTG TTTG
AAAATAAAACAACATTACCTG
TTAATG TAG CATTTG AG CTTTG G G CTAAGCG CAACATTAAACCAGTACCAG AG
GTGAAAATACTCAATAATTTG GGTGTG
G AC ATTG CTG CTAATACTGTG ATCTG G G ACTACAAAA G AG ATG CTCCAG CA CATATAT
CTACTATTG GTGTTTGTTCTATG
ACT G ACATAG CC AAG AAAC CAACTG AAAC G ATTTG TG CA C CACT CACT G TCTTTTTTG ATG
G TAG A G TTG ATG G TCAA G TA
GACTTATTTAG AAATG CCCGTAATG GTG TTCTTATTACAGAAG GTAGTGTTAAAG GTTTACAAC CATCTG
TAG GTCCCAAA
CAAG CTAGTCTTAATG GAGTCACATTAATTG GAG AAG CCG TAAAAAC ACAG TT CAATT ATTATAAG
AAAG TTGATG GTG TT
GTCCAACAATTAC CTG AAA CTTA CTTTACTCAG AG TAG AAATTTACAAG AATTTAAAC C CAG G AG
TC AAATG G AAATTG AT
TTCTTAGAATTAGCTATG GATGAATTCATTGAACG GTATAAATTAG AAG G CTATG
CCTTCGAACATATCGTTTATG G AG AT
TTTAGTCATAGTCAGTTAG GTG GTTTACAT CTACTG ATTG G A CTAG CTAAACGTTTTAAG G AATC AC
CTTTTG AATTAGAAG
ATTTTATTCCTATG G ACAG TA CAG TTAAAAACTATTTC ATAACAG AT G CG CAAACAG
GTTCATCTAAGTGTGTGTGTTCTGT
TATTG ATTTATTACTTG AT G ATTTTG TTG AAATAATAAAAT CC CAA G ATTTATCTG TA G
TTTCTAA G G TT GTC AAAG T G ACT
ATTG ACTATAC AG AAATTTCATTTATG CTTTG GTGTAAAGATG G C CATG TA G AAACATTTTAC
CCAAAATTACAATCTAG TC
AAG CGTG G CAACCG GGTGTTG CTATG CCTAATCTTTACAAAATG CAAAGAATG CTATTAG AAAAG TG
TG AC CTTCA AAATT
ATG GTG ATAGTG CAACATTACCTAAAG G CATAATGATGAATGTCG
CAAAATATACTCAACTGTGTCAATATTTAAACACAT
TAACATTAG CTG TAC C CTATAATAT G AG AG TTATAC ATTTT G GTG CTG G TTCTG AT AAAG G
AG TT G CAC C AG G TA CAG CTG
TTTTAAGACAGTG GTTG CCTACG G GTACG CT G CTTGTCGATTCAG ATCTTAATG ACTTTGTCTCTG
ATG CAGATTCAACTTT
G ATTG G TG ATTGTG CAACTG TA CATAC AG CT AATAAATG G G
ATCTCATTATTAGTGATATGTACGACCCTAAGACTAAAAA
TGTTACAAAAGAAAATG ACTCTAAAG AG G GTTTTTTCACTTACATTTGTG G GTTTATACAACAAAAG
CTAGCTCTTG GAG G
TTCCGTG G CTATAAAG ATA ACAG AA CATTCTTG GAATG CTG ATCTTTATAAG CT CATG GG AC
ACTTCG CATG GTG GACAG C
CTTTGTTACTAATGTGAATG CGTCATCATCTG AAG CATTTTTAATTG GATGTAATTATCTTG GCAAACCACG
C G AA CAAATA
G AT G GTTATGTCATG CAT G CAAATTACATATTTTG G AG G AATACAAATC CAATT C AG TT G
TCTTC CTATTCTTTATTTG AC AT
G AG TAAATTT C C C CTTAAATTAAG G GGTACTG CTGTTATGTCTTTAAAAGAAG
GTCAAATCAATGATATG ATTTTATCTCTT
CTTAGTAAAG G TAG A CTTATAATTAG AG AAAACAA CAG AG TTG TTATTTCTAG TG
ATGTTCTTGTTAACAACTAAACGAAC
AATGTTTGTTTTTCTTGTTTTATTG CCA CTAGT CTCTAG TC AG TG TG TTAAT CTTAC AAC CAG
AACT CAATTACCCCCTG CAT
ACA CTAATTCTTTCA CAC G T G GT G TTTATTAC CCTG ACAAA G TTTTCAG ATC CT CAG
TTTTAC ATTC AACTC AG GACTTGTTC
TTAC CTTTCTTTTC CAATG TTACTT G G TTC CAT G CTATACATGTCTCTGG G AC C AATG
GTACTAAG AG GTTTGATAACCCTGT
CCTACCATTTAATGATG GTGTTTATTTTG CTTCCACTG AG AAG TCTAACATAATAAG AG G CTG G
ATTTTTG GTACTACTTTA
GATTCG AAG AC C CAG TC C CTACTTATTG TTAATAAC G
CTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTTTGTAATG
ATCCATTTTTG G GTGTTTATTACCACAAAAACAACAAAAGTTGG ATG G AAAGTG AG TTCAG AG TTTATT
CTAGTG CG AATA
AUG CACTTTTGAATATGTCTCTCAG CCTTTTCTTATG G AC CTTG AAG G AAAACAG G
GTAATTTCAAAAATCTTAG G GAATT
TGTGTTTAAG AATATTGATG GTTATTTTAAAATATATTCTAAG CA CACG C CTATTAATTTAGTG CGT G
AT CTCCCT CAG G GT
TTTTCG GCTTTAG AACCATTG G TAG ATTTG CCAATAGGTATTAACATCACTAG GTTTCAAACTTTACTTG
CTTTA CATAG AA
G TTATTTG ACTC CT G GT G ATT CTTCTTCAGGTTG G A CAG CT G GT G CT G CAG
CTTATTATGTG G GTTATCTTCAACCTAG G AC
TTTTCTATTAAAATATAATG AAAATG G AAC CATTA CAG AT G CT G TAG ACT G TG CA CTTG AC
C CTC TCTCAG AAACAAAGTG
TAC G TT G AAAT C CTT CACTG TAG AAAAAG G AAT CTATC AAACTTCTAA CTTTAG AG TC
CAAC CAA CAG AATCTATTG TTAG A
TTTCCTAATATTACAAACTTGTG CCCTTTTG GTGAAGTTTTTAACG C CA C CA GATTTG CATCTGTTTATG
CTTG G AACAG GA
AG A G AAT CAG CAACTGTGTTG CT G ATTATTCTTT C CTATATAATTC C G CAT CATTTTC
CACTTTTAA G TG TTAT G G AG TG TCT
C CTA CTAAATTAAATG AT CTCT G CTTTACTAATGTCTATG CAG ATTC ATTT G TAATTAG AG GTG
ATG AAG T CAG AC AAATC G
CTC CA G G GCAAACTG G A AA G ATT G CT G ATTATAATTATAAATTA C CA G ATGATITTA CAG
G CTG CGTTATAG CTTG G AATT
CTAACAATCTTGATTCTAAG GTTG GTG G TAATTATAATTAC CT G TAT AG ATT G TTTAG G AAG
TCTAAT CTC AAAC CTTTT G A
GAG AG ATATTTCAACTGAAAT CTATC AG GCCG GTAG CA CAC CTTG TAATG GTG TT GAAG
GTTTTAATTGTTACTTTCCTTTA
CAATCATATG GTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAG AG TA G TA G TACTTTCTTTT G
AACTTCTACATG
CAC CAG CAACTGTTTGTG G AC CTAAAAAG T CTACTAATTTG
GTTAAAAACAAATGTGTCAATTTCAACTTCAATG GTTTAAC

AG G CA CA G GTGTTCTTACTGAGTCTAACAAAAAGTTTCTG CCTTTCCAACAATTTG G CAG A GACATTG
CTGA C ACTACTGA
TG CTGTC CGT G AT CCACAG ACACTTG AG ATTCTTG ACATTACACCATGTTCTTTTG GIG
GTGTCAGTGTTATAACACCAG GA
ACAAATACTTCTAACCAG G TT G CTGTTCTTTATCAG GATGTTAACTG C AC AGAAG TC CCTG TTG
CTATTCATG CAGATCAAC
TTACTCCTACTTG G CGTG TTTATTCTACAGGTTCTAATGTTTTTCAAACACGTG CAG G CTGTTTAATAG G
G G CT G AACAT G T
CAACAACTCATATG AG TGTGACATACCCATTG GTGCAG GTATATG CG CTAGTTATCAGACTCAG
ACTAATTCTCCTCG G CG
G G CACG TAGTG TAG CTAGTCAATCCATCATTG CCTACACTATGTCACTTG GTG CAG AAAATTC AG
TTG CTTACT CTAATAAC
TCTATTGCCATACCCACAAATTTTACTATTAGTGTTACCACAG AAATTCTAC CAG T G TCTATG A CCAAG A
CATC AG TA G ATT
GTACAATGTACATTTGTG G TGATTCAACTGAATG C AG CAATCTTTTGTTG CAATATG G CA G TTTTTG
TACAC AATTAAACCG
TG CTTTAACTG GAATAG CTG TTG AA CAAGAC AAAAACA CCCAAG AAGTTTTTG CA CAA G TCAAA
CAAATTTACAAAACACC
ACCAATTAAAGATTTTG GTG GTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAG CAAG AG G
TCATTTATTG AA
G AT CTAC TTTTC AAC AAAGTG ACACTTG CAGATG CTG GCTTC AT CAAACAATATG GT G
ATTGCCTTG GTGATATTG CTG CIA
GAG AC CT CATTT G TG CACAAAAGTTTAACG G CCTTACTGTTTTG CCACCTTTG CTCACAGATG
AAATG AUG CTCAATACAC
TT CTG CACTGTTAG CG G GTACAATCACTTCTG GTTG GACCTTTG GTG CAGGTGCTG
CATTACAAATACCATTTG CTATG CA
AATG GCTTATAG GTTTAATG GTATTG G AG TTACA CAG AAT GTTCTCTATG AG
AACCAAAAATTGATTG CCAACCAATTTAA
TAG TG CT ATTG G CAAAATTCAAGACTCACTTTCTTCCACAG CAAGTG CACTTG GAAAACTTCAAGATGTG
GTCAACCAAAA
TG CACAAG CTTTAAACACG CTTGTTAAACAACTTAG CT C CAATTTT G GTG
CAATTTCAAGTGTTTTAAATG ATATC CTTT CAC
GTCTTG ACAAAGTTG AG G CTGAAGTG CAAATTGATAG G TT G ATCACAG G CAGACTTCAAAGTTTG
CA G ACATATGTG ACT
CAAC AATTAATTA G AG CTG CAG AAATC AG AG CTTCTG CTAATCTTG CTG CT ACTAAAATG T
CAG AG TGTGTACTTG GACAA
TCAAAAAG AG TTG ATTTTTG TG GAAAG G G CTATCAT CTTATGTCCTTC CCTC AG TC AG CAC
CTCATG G TG TAG TCTT CTTG C
ATG TG A CTTAT G TC CCTG CACAAG AAAAG AACTTCACAACTG CTCCTG CCATTTGTCATGATG
GAAAAG CAC A CTTT CCT C
GTGAAG GTGTCTTTGTTTCAAATG G CA CACA CTG GTTTGTAACACAAAG GAATTTTTATG AAC CAC
AAATCATTACTACAG
ACAACACATTTGTGTCTG G TAACT G TG ATG TT G TAATAG G AATTG TCAA CAACAC AG TTTATG
ATCCTTTG CAACCTG AATT
AGA CTCATTCAAG GAG G AG TTAG ATAAATATTTTAAGAATCATACATCACCAG ATGTTGATTTAG GIG
ACATCTCTG G CAT
TAATG CTTCAGTTGTAAACATTCAAAAAG AAATTGACCG CCT CAATG AG GTTG CCAAGAATTTAAATG
AATCTCTCATCGA
TCTCCAAG AACTTG GAAAGTATGAG CAGTATATAAAATG G CCATGGTACATTTGG CTAG GTTTTATAG
CTG G CTTGATTG C
CATAGTAATG GTG ACAATTATG CTTTG CTGTATG ACCAGTTG CTG TAG TTG TCTCAAG GG CTG TT
G TT CTTG TG G ATCCTG C
TG CAAATTTG ATG AAG ACGACTCTG AG CCAGTGCTCAAAG G AG TCAAATTACATTACAC ATAAACG
AACTTATG GATTTGT
TTATG AG AATCTTCACAATTG G AA CTG TAACTTTG AAG CAAG GTG AAATCAAG GATG
CTACTCCTTCAGATTTTGTTCG CG
CTACTG CAACG ATACC GAT ACAAG CCTCACTCCCTTTCG G ATG G CTTATTGTTG G CGTTG
CACTTCTTG CTGTTTTTCAG AG
CG CTTCC AAAATC ATAACC CTCAAAAAG AG ATG G CAACTAG CACTCTCCAAG G
GTGTTCACTTTGTTTG CAACTTG CTG TT
G TTG TTTG TAACAG TTTA CTCAC A CCTTTTG CTCGTTG CTG CTG GCCTTG AAG
CCCCTTTTCTCTATCTTTATG CTTTAGTCTA
CTTCTT G CAG AG TATAAA CTTTG TAAG AATAATAAT G AG G CTTTG G CTTTG CT G GAAATG
CCG TTCCAAAAACCCATTACTT
TAT G ATG CCAACTATTTTCTTTG CTG G
CATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGT
CATTACTTCAG GTG ATG G C ACAA CAAG T CCTATTTC TG AA CATG ACTA C CAG ATTG G
TGGTTATACTG AAAAATG G G AATC
TG G AG TAAAAG ACT G TG TTG TATTAC ACAG TTACTTCACTTCAG ACTATTACC AG CT G
TACTCAACTCAATTG A G TAC AG AC
ACT G GTGTTG AACATG TTA C CTTCTTCAT CTACAATAAAATTG TTG AT G AG C CTG AA GAACAT
G TC CAAATT CACACAATCG
ACGTTTCATCCG G AG TTG TTAAT CCAG TAATG GAACCAATTTATG ATG AAC CGACG ACGACTACTAG
CGTG CCTTTGTAAG
CAC AAG CTG ATG AG TACG AACTTATG TACTC ATTC G TTT CG G AAG A G AC AG G TACG
TTAATAG TTAATAG CGTACTTCTTT
TT CTTG CTTTCGTG GTATTCTTG CTAGTTACACTAG CCATCCTTACTG CG CTTC GATTGTGTG
CGTACTG CTG CAATATTG TT
AACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTC GTGTTAAAAATCTGAATTCTTCTAGAGTTCCTG
ATCTTCTG GT
CTAAACGAACTAAATATTATATTAGTTTTTCTGTTTG GAACTTTAATTTTAG CCATG G CAG ATTCCAACG
GTACTATTACCGT
TG AAGAG CTTAAAAAG CTCCTTGAACAATG GAACCTAGTAATAG GTTTCCTATTCCTTACATG
GATTTGTCTTCTACAATTT
G CCTATG CCAACAGG AATAG GTTTTTGTATATAATTAAGTTAATTTTCCTCTG G CT G TTATG G
CCAGTAACTTTAG CTT G TT
TT G TG CTTG CTG CTGTTTACAGAATAAATTG GATCACCG GTG G AATTG CTATCG CAATGG CTTG
TCTTG TAG G CTTG AT G T
G G CTCAG CTACTTCATTG CTT CTTTC AG ACTG TTTGCG CGTACG CGTTCCATGTG
GTCATTCAATCCAGAAACTAACATTCT
TCTCAACGTG C CA CTCCATG G CACTATTCTG ACC AG ACC G CTTCTAG AAAGTGAACTCGTAATCG G
AG CTGTG AT CCTTCG
TG GACATCTTCGTATTG CTG G A CACCAT CTAG GACG CTGTGACATCAAG G AC CTG CCTAAAG
AAATCACTGTTG CTACATC
ACG AACG CTTTCTTATTACAAATTG G GAG CTTCG CAG CGTGTAG CAG GTGACTCAG GTTTTG CT G
CATACAGTCGCTACAG
GATTGG CAACTATAAATTAAACACAG ACCATTCCAG TAG C AG T G ACAATATT G CTTTG CTTG
TACAG TAAG T G AC AACAG A
TG TTTC ATCTCG TTG ACTTTC AG GTTACTATAGCAG AG ATATTACTAATTATTATG AG G
ACTTTTAAAGTTTCCATTTG GAAT
CTTG ATTA CATC ATAAA C CTCATAATTA AAAATTTATCTAA GT CACTAA CTG A G AATAA ATATT
CTCAATTA G ATGAAG AG C
AACCAATG GAG ATTGATTAAACGAACATGAAAATTATTCTTTTCTTG G CACTGATAACACTCG CTACTTG TG
AG CTTTATCA
CTA C CAA G AG TG TG TTAG A G G TA CAA CAG TACTTTTAAAAGAACCTTG CT CTTC TG G
AACATA CG AG G G CAATTCACCATT
TCATCCTCTAG CTGATAACAAATTTG CACTGACTTG CTTTAG CA CTCAATTTG CTTTTGCTTGTCCTG AC
GG CG TAAAAC AC
GTCTATCAGTTACGTG CCAG ATC AG TTTCACCTAAA CTGTT CATCAG ACAAG AG G AAGTTCAAG
AACTTTACTCTCCAATTT

TTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATTGAACTTTCATTA
ATT
GACTTCTATTTGTG CTTTTTAG CCTTTCTG CTATTCCTTGTTTTAATTATG CTTATTATCTTTTG
GTTCTCACTTGAACTG CAA
GATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTGCAT
TTC
ACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTCACTTCTATTC
TAA
ATG GTATATTAGAGTAG GAG CTAGAAAATCAG CACCTTTAATTGAATTGTG CGTG GATGAGG
CTGGTTCTAAATCACCCA
TTCAGTACATCG ATATCG GTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTG CCAGG
AACCTAAATTGG GTAGTCTT
GTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACGAACA
AAC
TAAAATGTCTGATAATGGACCCCAAAATCAG CGAAATG CACCCCG CATTACG TTTG GIG GACCCTCAG
ATTCAACTG G CA
GTAACCAGAATGGAGAACGCAGTGGGGCGCGATCAAAACAACGTCG
GCCCCAAGGTTTACCCAATAATACTGCGTCTTG
GTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAGGCGTTCCAATTAACACCAATAGC
AG
TCCAGATGACCAAATTGGCTACTACCGAAGAGCTACCAGACGAATTCGTGGTG
GTGACGGTAAAATGAAAGATCTCAGTC
CAAGATGGTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATG
G
GTTG CAACTGAG G G AG CCTTGAATACACCAAAAGATCACATTG G CACCCG CAATCCTG CTAACAATG
CTG CAATCGTG CT
ACAACTTCCTCAAG GAACAACATTG CCAAAAG G CTTCTACGCAGAAG G GAG CAGAG G CGG CAGTCAAG
CCTCTTCTCGTT
CCTCATCACGTAGTCG CAACAG TTCAAGAAATTCAACTCCAG G CAG CAG TAG G G
GAACTTCTCCTGCTAG AATG G CTG GC
AATGGCGGTGATGCTGCTCTTGCTTTGCTGCTGCTTGACAGATTGAACCAGCTTGAGAGCAAAATGTCTGGTAAAGGCC
A
ACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGG
CTTCTAAGAAGCCTCGGCAAAAACGTACTGCCACTA
AAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGGAACTAAT
C
AGACAAGGAACTGATTACAAACATTG GCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAG
CGTTCTTCGGAATGTCGCGC
ATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGATCCAAATT
T
CAAAGATCAAGTCATTTTGCTGAATAAG
CATATTGACGCATACAAAACATTCCCACCAACAGAGCCTAAAAAGGACAAAA
AGAAG AAG G CTGATGAAACTCAAG CCTTACCG CAGAGACAGAAGAAACAG CAAACTGTGACTCTTCTTCCTG
CTG CAGAT
TTGGATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAG
GCCTAAACTCATGCAGACCACACA
AGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTA
ACT
ACATAG CACAAGTAGATGTAGTTAACTTTAATCTCACATAG CAATCTTTAATCAGTGTGTAACATTAG G GAG
GACTTG AAA
GAG CCACCACATTTTCACCGAG GCCACG CG G AGTACGATCG AGTGTACAGTGAACAATG CTAG G GAG
AGCTGCCTATAT
G GAAG AG CCCTAATGTGTAAAATTAATTTTAGTAGTG CTATCCCCATGTGATTTTAATAG CTTCTTAG GAG
AATGACAAAA
SEQ ID NO: 13 >Severe acute respiratory syndrome coronavirus 2 orf1ab polyp rote in of isolate hCoV-19/Fra nce/I D F0372-is1/2020 M ESLVPGFNE KTHVQLSLPVLQVRDVLVRG FGDSVEEVLSEARQHLKDGTCG LVEVEKGVLPQLEQPYVF I
KRSDARTAPHG H
VMVE LVAELE GI QYG RSG ETLGVLVP HVG E I PVAYRKVLLRKNG NKGAGG HSYGADLKSF DLG
DELGTDPYE DFQENWNTKH
SSGVTR ELM RE LNGGAYTRYVDNNFCGP DGYPLECIKDLLARAG KASCTLSEQLDF I DTKRGVYCCRE HE
H EIAWYTE RSEKSYE
LQTP F El K LAKKF DTF NG E CP N FVFP LNSI I KTI QPRVEKKKLDGF M G RI RSVYPVASPN
ECNQMC LSTLM KC DHCG ETSWQTG
DFVKATC E FCGTE N LTKEGATTCGYLPQNAVVKIYCPACH NSEVG P E HSLAEYH NESGLKTI LR KGG
RTIAFGGCVFSYVG CH NK
CAYWVPRASAN IGCNHTGVVGEGSEG LND N LLEI LQKEKVN IN IVG DFKLNE EIAI I
LASFSASTSAFV ETVKGLDYKAF KQIVESC
GNF
KVTKGKAKKGAWNIGEQKSILSPLYAFASEAARVVRSIFSRTLETAQNSVRVLQKAAITILDGISQYSLRLIDAM M
FTSDLAT
NN LVVMAYITGGVVQLTSQWLTN I FGTVYE KLKPVLDWL EE KF KEG VE F LR DGWEIVKFISTCAC
EIVGG QIVTCAKE I KESVQT
F FKLVNKFLALCADSI I IG GAKLKALN LG ETFVTHSKG LYR KCVKSREETGLLM PLKAPK El I F
LEG ETLPTEVLTE EVVLKTG D LQP L
E QPTSEAVEAP LVGT PVCI NG LM LLEI KDTEKYCALAP NM MVTN NTFTLKGGAPTKVTFG DDTVI
EVQGYKSVN ITFE LDE R I DK
VLNEKCSAYTVE LGTEV NE FACVVADAVIKTLQPVSELLTPLG I D LD EWSMATYY LF DESG
EFKLASHMYCSFYPPDED E EEG DC
E E E EF E PSTQYEYGTE D DYQGKP LE FGATSAALQPE EEQEEDWLDD DSQQTVGQQDGSE
DNQTTTIQTIVEVQPQLE ME LTP
VVQTIEVNSFSGYLKLTDNVYIKNADIVE EAKKVKPTVVVNAANVYLKHGGGVAGALNKATNNAMQVESD DYIAT
NG PLKVG
GSCVLSGHNLAKHCLHVVG PNVNKG EDIQLLKSAYENF NQH EVLLAPLLSAG I FGAD PI HS
LRVCVDTVRTNVYLAVF DKN LYD
KLVSSFLE M KSEKQVEQKIAEI PK E EVKP FITESKPSVEQRKQDDKKIKACVE
EVTTTLEETKFLTENLLLYI DING NLHPDSATLVSD
I DITF LKKDAPYI VG DVVQEGVLTAVVI PTKKAGGTTEM LAKALRKVPTDNYITTYPGQG LNGYTVE
EAKTVLKKC KSAFYILPSI IS
NEKQEI LGTVSWN LREMLAHAE ETRKLM
PVCVETKAIVSTIQRKYKGIKIQEGVVDYGARFYFYTSKTTVASLINTLN DLN ETLVT
M PLGYVTHG LN LE EAARYM RSLKVPATVSVSSPDAVTAYNGYLTSSSKTPE EH F I ETISLAG
SYKDWSYSG QSTQLG I E FLKRG D
KSVYYTSN PTTFH LDG EVITF D NLKTLLSLR EVRTI KVFTTVD N IN LHTQVVD MSMTYGQQFG PTY
LDGADVTKI KPH NS H EG KT
FYVLPNDDTLRVEAFEYYHTTDPSF LGRYMSALN HTK KWKYPQVNGLTSIKWADNNCYLATALLTLQQI ELK F
N PPALQDAYYR
ARAGEAAN FCALILAYCNKTVGE
LGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQFKKGV
QI PCTCGKQATKYLVQQESPFVM MSAPPAQYELKHGTFTCASEYTGNYQCG HYKHITSKETLYCI
DGALLTKSSEYKGPITDVFY
KENSYTTTI KPVTYKLDGVVCTEI DP KLD NYYKKDNSYFTEQPI DLVPNQPYPNASFDNFKFVCD NI
KFADDLNQLTGYKKPASRE
LKVTFF PDLNGDVVAI DYKHYTPSF KKGAKLLH KPIVWHVNNATNKATYKP NTWC I RC
LWSTKPVETSNSF DVLKSE DAQG MD

N LACE DLKPVSE EVVEN PTIQKDVL ECNVKTTEVVG D II LKPANNS LKITE EVG
HTDLMAAYVDNSSLTIKKPN E LSRVLG LKTLAT
HGLAAVNSVPWDTIANYAKPFLNKVVSTTTNIVTRCLNRVCTNYM PYFFTLLLQLCTFTRSTNSRIKASM
PTTIAKNTVKSVGKF
CLEASF NYLKSPN FSKLI NI IIWFLLLSVCLGSLIYSTAALGVLMSN LGM
PSYCTGYREGYLNSTNVTIATYCTGSIPCSVCLSG LDSL

NLVQMAPISAM VRMY
IT FASFYYVWKSYVHVVDGCNSSTCM MCYKRNRATRVECTTIVNGVR RSFYVYANGG KG FCKLH
NWNCVNCDTFCAGSTF IS
DEVARDLSLQFKRPINPTDOSSYIVDSVTVKNGSIHLYFDKAGQKTYERHSLSH FVN LDN LRAN NTKGS LP
INVIVFDG KS KCE ES
SAKSASVYYSQLMCQP I LLLDQALVSDVG DSAEVAVKM FDAYVNTFSSTFNVPM E KLKTLVATAEAE
LAKNVSLD NVLSTF ISAA
ROG FVDSDVETKDVVECLKLSHQSDI EVTGDSCN NYM LTYN KVE N MTP RDLGACI DCSARH I
NAQVAKSH NIALIWNVKDF M
SLSEQLRKQIRSAAKKN NLPFK LICATTRQVVNVVITKIALKGG KIVN NWLKQLI KVTLVFL FVAAI
FYLITPVHVMSKHTDFSSE I I
GYKAI DGGVTRDIASTDTCFAN K HADFDTW FSQRGGSYTNDKACP LIAAVITREVG FVVPG
LPGTILRTTNGD F LH FLPRVFSAV
GNICYTPSKLIEYTDFATSACVLAAECTIFKDASGKPVPYCYDTNVLEGSVAYESLRPDTRYVLM
DGSIIQFPNTYLEGSVRVVTTF
DSEYCRHGTCERSEAGVCVSTSG RWVLN NDYYRSLPG VFCGVDAVN LLTN M
FTPLIQPIGALDISASIVAGGIVAIVVTCLAYYF
M RFRRAFG EYSHVVAFNTLLFLMSFTVLCLTPVYSFLPGVYSVIYLYLTFYLTNDVSFLAHIQWMVM
FTPLVPFWITIAYIICISTK
H FYW F FSNYLKRRVVFNGVSFSTFEEAALCTF LLN KE MYLKLRSDVLLP LTQYN RYLALYNKYKYFSGAM
DTTSYR EAACCH LAK
ALN DFSNSGSDVLYQPPQTSITSAVLQSGFR KMAFPSG KVEGC MVQVTCGTTTLNG LW
LDDVVYCPRHVICTSED M LN P NYE
DLLIRKSN HNFLVQAG NVQLRVIG HSMQNCVLKLKVDTANPKTP KYKFVRIQPGQTFSVLACYNGSPSG
VYQCAM RPNFTI KG
SF LNGSCGSVG F NI DYDCVSFCYM H H M ELPTGVHAGTDLEGNFYG PFVDRQTAQAAGTDTTITVN
VLAW LYAAVI NG DRWF
LNRFTTTLNDFN LVAMKYNYE PLTQDHVDILG PLSAQTGIAVLDMCASLKE LLQNG M NG RTILGSALLE
DE FTPF DVVRQCSGV
TFQSAVKRTI KGTH HW LLLTI LTSLLVLVQSTQWSLFF F LYE NAFLPFAMGIIAMSAFAM M
FVKHKHAFLCLFLLPSLATVAYFN
MVYMPASWVM RI MTW LDMVDTSLSGF KLKDCVMYASAVVLLI LMTARTVYDDGAR RVWT LM
NVLTLVYKVYYG NALDQA
ISMWALIISVTSNYSGVVTTVM FLARG IVF MCVEYCPIFFITGNTLQCIMLVYCFLGYFCTCYFG LFCLLN
RYFRLTLGVYDYLVST
QEF RYM NSQG LLPPKNSI DAF KLN I KLLGVGG
KPCIKVATVQSKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHN DI LLA
KDTTEAFE KM VSLLSVLLSMQGAVDI N KLCEEMLDN RATLQAIASEFSSLPSYAAFATAQEAYEQAVANG
DSEVVLKKLKKSL N
VAKSEFDRDAAMQRKLEKMADQAMTQMYKQARSEDKRAKVISAMQTMLFTMLRKLDN DALN NI I N
NARDGCVPLNIIP LT
TAAKLMVVI PDYNTYKNTCDGTTFTYASALWEIQQVVDADSKI VQLSEISM
DNSPNLAWPLIVTALRANSAVKLQNN ELSPVAL
RQMSCAAGTTQTACTDDNALAYYNTTKGG RFVLALLSDLQDLKWARFPKSDGTGTIYTELE PPCRFVTDTPKG P
KVKYLYFI KG
LNNLNRG MVLGSLAATVRLQAG NATEVPANSTVLSFCAFAVDAAKAYKDYLASGGQPITNCVKM
LCTHTGTGQAITVTPEAN
M DQESEGGASCCLYCRCHIDHPNPKGFCDLKGKYVQIPTTCANDPVG FTLKNTVCTVCGMWKGYGCSCDQLREPM
LQSADA
QSF LNG FAV
SEQ ID NO: 14 >Protein \S_Human \2019-nCoV (Sprotein_hCoV19FranceIDF0372is12020) M FVF LVLLP LVSSQCVN LTTRTQLP PAYTNSFTRGVYYPDKVFRSSVLHSTQDLF LPFFSNVTWF HAI
HVSGTNGTK RFDN PVLP
F N DGVYFASTEKSN II
RGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWMESEFRVYSSANNCTF EY
VSQPFLM DLEGKQG NFKN LRE FVF KN I DGYFKIYSKHTP I N LVR DLPQG FSALEP LVDLPIGIN
ITRFQTLLALHRSYLTPGDSSSG
WTAGAAAYYVGYLQPRTFLLKYNE NGTITDAVDCALDPLSETKCILKSFTVEKGIYQTSN FRVQPTESIVRFP
NITNLCPFG EVFN
ATRFASVYAWN RKRISNCVADYSFLYNSASFSTFKCYGVSPTKLNDLCFTNVYADSFVIRG
DEVROJAPGOTGKIADYNYKLPDD
FTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQP
YRVVV
LSFELLHAPATVCG PKKSTNLVKNKCVN FN F NG LTGTGVLTESN KKF LPFQQFG
RDIADTTDAVRDPQTLE I LDITPCSFGGVSVI
TPGTNTSNQVAVLYQDVNCTEVPVAI HADQLTPTVVRVYSTGSNVFQTRAGCLIGAE
HVNNSYECDIPIGAGICASYQTQTNSP
RRARSVASQS1lAYTMSLGAENSVAYSN NSIAIPTNFTISVTTEILPVSMTKTSVDCTMYICG
DSTECSNLLLQYGSFCTQLNRALT

DCLGDIAARDLICAQKF
NG LTVLPPL LTDE M IAQYTSALLAGTITSGWTF GAGAALQI PFAM QMAYRFNG
IGVTQNVLYENQKLIANQF NSAIG KIQDSLS
STASALG KLQDVVNQNAQALNTLVKQLSSN FGAISSVLN D I LSR LDKVEA EVQI D RLITG R
LQSLQTYVTQQLIRAAEI RASAN LA
ATKMSECVLGQSKRVDFCG KGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDG
KAHFPREGVFVSNGTHWFVTQ
RNFYEPQIITTDNTFVSG NCDVVIG IVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISG I
NASVVNIQK El DRLNEVAKN
LN ESLI DLQELG KYEQYI KWPWYIW LG FIAG LIAIVM VTI M
LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
SEQ ID NO: 15 >hCoV-19/Austria/CeMM0360/20201EPUSL_43812312020-04-05 NN NNNN NNNNN NNNN NNNNNNNNN NNNN
NNACCAACCAACTTTCGATCTCTTGTAGATCTGITCTCTAAACGAACTT
TAAAATCTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGA
CA
GGACACGAGTAACTCGTCTATCTTCTGCAGG CTG CTTAC G GTTTC G TC CG TGTTG CAG CC G
ATCATCAG CACATCTAGGTT
TTGTCCG GGTGTG ACCGAAAGGTAAGATGGAG
AGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTG
CCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGGCTTTGGAGACTCCGTGGAGGAGGTCTTATCAGAGGCACGTCAAC
A

TCTTAAAG ATG G CACTTGTG G CTTAGTAGAAGTTG AAAAAG G CG TTTTG CCT CAACTTG AA CAG
C CCTATGTG TTC AT CAA
ACGTTCG GAT G CTCG AACTG CA CCT CATG G T CAT GTTATG GTTGAG CTG GTAG CAG AACTC
GAAG G CATTCAGTACG GTC
GTAGTG GTG AG ACACTTG GTGTCCTTGTCCCTCATGTG GGCGAAATACCAGTG G CTTACCG CAAG G
TTCTTCTTCGTAAG A
ACG GTAATAAAG G AG CTGGTG GCCATAGTTACG GCG CCG ATCTAAAGTCATTTGACTTAG G CG ACG
AG CTTG G CA CTG AT
CCTTATGAAG ATTTT CAAGAAAACT G GAACACTAAACATAG CA G TG GTGTTACCCGTG
AACTCATGCGTG AG CTTAACG G
AGG G G CATACACTCG CTATGTCG ATAACAACTTCTGTG G CCCTGATG GCTAC CCTCTTGAGTG
CATTAAAGACCTTCTAG C
ACGTGCTGGTAAAG CTTCATG CACTTTGTC CG AA CAACTG GACTTTATTG ACACTAAG AG G G
GTGTATACTGCTGCCGTG A
ACAT G AG CATGAAATTG CTTG GTACACG GAACGTTCTG AAAAG A G CTATG AATTG
CAGACACCTTTTGAAATTAAATTG G
CAAAGAAATTTG ACACCTTCAATG G G
GAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAG
G GTTGAAAAGAAAAAG CTTGATG G CTTTATG G G TAG AATTC G ATCTG TCTATCCAGTTG
CGTCACCAAATG AATG CAACC
AAATGTG CCTTTCAACTCTC ATG AAGTGTG AT CATTGTG GTG AAACTTCATG G CAGACG G G
CGATTTTGTTAAAG CCACTT
G CGAATTTTG TG G CACTG AG AATTTG ACTAAAG AAG GTG
CCACTACTTGTGGTTACTTACCCCAAAATG CTGTTGTTAAAA
TTTATTGTCCAG CAT GTCA CAATT CAG AAG TAG G ACCTG AG CATAGTCTTG CCG AATACCATAATG
AATCTG G CTTGAAAA
CCATTCTTCGTAAG G GTG GTCG CACTATTG CCTTTG G AG G CTGTGTGTTCTCTTATGTTG
GTTGCCATAACAAGTGTG CCTA
TTG G GTTCCACGTG CTAG CGCTAACATAGGTTGTAACCATACAG GTGTTGTTG G AG AAG GTTCCG AAG
GTCTTAATGACA
ACCTTCTTG AAATACT CCAAAAA G AG AAAGT CAACAT CAATATTGTTG G TG ACTTTAAACTTAATG
AAG AG ATCG CCATTA
TTTTG G CATCTTTTTCTG CTTCCACAAGTG CTTTTGTG G AAA CTGT G AAAG GTTTG GATTATAAAG
CATTCAAACAAATTGT
TG AATCCTGTG GTAATTTTAAAGTTACAAAAG GAAAAG CTAAAAAAG GTG CCTG GAATATTG GTG
AACAG AAATCAATAC
TG AGTCCTCTTTATG CATTTG CATCAG AG G CTG CTCGTGTTGTACGATCAATTTTCTCCCG CACTCTTG
AAACTGCTCAAAA
TT CTGTGCGTGTTTTACA GAAG G CCG CTATAACAATACTAG ATGG AATTTCACAGTATTCACTG AG
ACTCATTG ATG CTAT
G AT GTT C ACAT CTG ATTTG G CTACTAACAATCTAGTTGTAATGG C CTACATTA CA G GTG GTG
TTG TTCAG TTG A CTTC G CAG
TG G CTAACTAACATCTTTG G CACTGTTTATGAAAAACTCAAACCCGTCCTTG ATTG G CTTGAAG AG AAG
TTTAAG GAAG GT
GTAG AG TTTCTTAG AG ACG GTTG G GAAATTGTTAAATTTATCTCAACCTGTG CTTGTGAAATTGTCG
GTG GACAAATTGTC
ACCTGTG CAAAG GAAATTAAGG AG AG TGTT CAG AC ATTCTTTAA G CTT GTAAATAAATTTTTG G
CTTTGTGTG CTG A CTCT
ATCATTATTG GTG GAG CTAAACTTAAAG CCTTGAATTTAG GTGAAACATTTGTCACG CACTCAAAG G G
ATTGTAC AG AAA
GTGTGTTAAATCCAG AG AAG AAACTG G CCTACTCATG CCTCTAAAAG CCCCAAAAGAAATTATCTTCTTAG
AG G G AG AAA
CACTTCCC ACAG AAGTG TTAA CAG AG GAAGTTGTCTTG
AAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAA
G CTGTTG AAG CTCCATTG G TT G GTACACCAGTTTGTATTAAC G GG CTTAT G TT G
CTCGAAATCAAAG ACACAGAAAAGTAC
TGTG CC CTTG CACCTAATATG ATG GTAACAAACAATACCTTCACACTCAAAG G CG GTG
CACCAACAAAGG TTACTTTTG GT
G AT G ACACTGTG ATAG AAGTG CAAG GTTA CAAG AG TGT G AATATCACTTTTG AACTTGATG
AAAG G ATTG ATAAAG TACT
TAATG AG AAGTG CTCTG CCTATACAGTTGAACTCG GTACAGAAGTAAATGAGTTCG CCTGTGTTGTG G
CAG ATG CTGT CA
TAAAAACTTTG CAACCAGTATCTGAATTACTTACACCACTG G G CATTGATTTAGATGAGTG G AG TATG G
CTACATACTACT
TATTTG ATG AG TCT G GTG AGTTTAAATTG G CTTC AC ATATGTATTGTTCTTTTTACCCTC CAG ATG
AG GAT GAAG AAG AA G
GTGATTGTG AAG AAG AAG AG TTTG AG CCATCAACTCAATATG AGTATG GTACTG
AAGATGATTACCAAG GTAAACCTTTG
GAATTTG GTG CCACTTCTG CTG CTCTT CAACCT G AAG AAG AG CAAG AA G AAG ATTG GTTAG
ATGATGATAGTCAACAAAC
TGTTG GTCAACAAGACG G CA GTG AG G ACAATCAGACAACTACTATTCAAACAATTGTTG AGG
TTCAACCTC AATTA G AGA
TG GAACTTACACCAGTTGTTCAG ACTATTGAAGTGAATAGTTTTAGTG GTT ATTTAAAACTTACT G AC AAT
GTATACATTAA
AAATGCAG ACATTGTG GAAG AAG CTAAAAAG GTAAAACCAACAGTG GTT GTTAATGC AG
CCAATGTTTACCTTAAACATG
GAG GAG GTGTTG CA G GAG CCTTAAATAAG G CTACTAACAATG CCATG
CAAGTTGAATCTGATGATTACATAG CTACTAAT
G GACCACTTAAAGTG G GTG GTAGTTGTGTTTTAAG CG G AC ACAATCTTG
CTAAACACTGTCTTCATGTTGTCG G CCCAAAT
GTTAACAAAG GTG AAG ACATTCAACTTCTTAAG AG TG CTTATG AAAATTTTAATCAG CAC
GAAGTTCTACTTG CACCATTAT
TAT CAG CTG GTATTTTTG GTG CTG ACCCTATACATTCTTTAAG AGTTTGTGTAG ATACTGTTCG
CACAAATGTCTACTTAGC
TG TCTTTG ATAAAAAT CTCTATG AC AAACTT GTTT CAA G CTTTTTG GAAATGAAG AGTG AAAAG C
AAGTT GAAC AAAAG AT
CG CTG A G ATT CCTAAAGAG G AAGTTAAG C C ATTTATAACT G AAA GTAAACCTT CA GTTG AA
CAG AG AAAACAAG AT G ATA
AGAAAATC AAA G CTTGTGTTGAAGAAGTTACAACAACTCTG G AA G AAACTAAGTTC CTC ACAG
AAAACTTGTTACTTTATA
TT G ACATTAAT G G CAATCTTCATC CAG ATTCTG
CCACTCTTGTTAGTGACATTGACATCACTTTCTTAAAGAAAGATG CTCC
ATATATAGTG G GTG ATGTTGTT CAA G AG G GTGTTTTAACTG CTGTG GTTATACCTACTAAAAAG G
CTG GTG G CACTACTG
AAATGCTAG CGAAAGCTTTG AG AAAAGTG CCAACAG ACAATTATATAACCACTTACCCG G GTC AG G
GTTTAAATG GTTAC
ACT GTAG AG G AG G CAAAG AC AGTG CTTAAAAAGTGTAAAAGTG
CCTTTTACATTCTACCATCTATTATCTCTAATG AG AAG
CAA G AAATTCTT G GAACTGTTTCTTG G AATTTG CG AG AAATG CTTG CACATG CAGAAG AAACACG
CAAATTAATG C CT G TC
TGTGTG G AAA CTAAA G CCATAGTTTCAACTATACAG C G TA AATATAA G G GTATTA AAATAC AAG
AG GGIGTG GTTGATTA
TG GTG CTAG ATTTTACTTTTACACCAGTAAAACAACTGTAG CGTCACTTATCAACACACTTAACG
ATCTAAATG AAACTCTT
GTTACAATG CC ACTTG G CTATGTAACACATG G CTTAAATTTG G AA G AAG CTG CTCG G TATATG
AG ATCTCTC AAA GTG CCA
G CTACAGTTTCTGTTTCTTCACCTG ATG CTGTTACAG CGTATAATG
GTTATCTTACTTCTTCTTCTAAAACACCTGAAG AACA
TTTTATTGAAACCATCTCACTTG CTG G TT CCTATAAAG ATTGGTCCTATTCTG GACAATCTACACAACTAG
GTATAGAATTTC

TTAA G AG AG GT G ATAAAAG T G TATATTA CACTA G TAAT CCTA C CACATTCC A CCTAG ATG
GTG AAGTTATCACCTTTG ACA
ATCTTAAG AC ACTTCTTTCTTTG AG AG AAG TG AG G ACTATTAAG G TGTTTAC AA CAG TAG AC
AACATTAACCTCCAC AC G C
AAGTTGTGGACATGTCAATGACATATG G ACAACAGTTTGGTCCAACTTATTTG GATG G AG
CTGATGTTACTAAAATAAAAC
CTCATAATTCACATGAAG GTAAAACATTTT ATG TTTTACCTAATG ATG ACACTCTA CG TG TTG AG G
CTTTTGAGTACTACCA
CACAACTGATCCTAGTTTTCTG G GTAG GTACATGTCAG CATTAAATCACACTAAAAAGTG
GAAATACCCACAAGTTAATG G
TTTAACTTCTATTAAATG G G CAGATAACAACTGTTATCTTG CCACTG CATTGTTAACACTCCAACAAATAG
AG TTG AAGTTT
AAT CCAC CT G CTCTACAAGATG CTTATTACAG AG CAA G G G CTG GTG AAG CTG
CTAACTTTTGTG C ACTTATCTT AG CCTACT
G TAATAAG ACAG TAG GT G AG TTAG G TG AT G TTAG AG AAACAAT G AG TTACTTG TTT CAA
C ATG CCAATTTAGATTCTTG CA
AAAG AGTCTTGAACGTG GTG TGTAAAACTTGTG G ACAAC AG CAG ACAACCCTTAAG G GTGTAG AAG
CTGTTATGTACATG
G G CACACTTTCTTATGAACAATTTAAG AAA G GT G TTC AG ATACCTT G TAC G TG T G
GTAAACAAG CTACAAAATATCTA G TA
CAA CAG G AGTCACCTTTTGTTATG ATGTCAG CACCACCTG CT CAGTATGAACTTAAG CATG
GTACATTTACTTGTG CTAGTG
AG TACACTG GTAATTACCAGTGTG GTCACTATAAACATATAACTTCTAAAG AAACTTTGTATTG CATAGACG
GTG CTTTACT
TAC AAAG TCCTC A G AATAC AAAG GTCCTATTACG G AT G TTTT CTACAAAG AAAACAG TTACAC
AACAAC CATAAAACCAG T
TACTTATAAATTGGATG G TG TT G TTTG TACAG AAATTGACCCTAAGTTG G ACAATTATTATAAG AAAG
AC AATTCTTATTTC
ACAG AG CA ACCAATTG ATCTTG TAC CAA ACCAAC CATATC CAAAC G CAAG CTTCG ATAATTTTAA
G TTT G TAT G TG ATAAT
ATCAAATTTG CT G ATG ATTTAAACCAGTTAACTG GTTATAAG AAACCTG CTTCAAG AG AG
CTTAAAGTTACATTTTTCCCTG
ACTTAAATG GTGATGTGGTG G CTATTGATTATAAACACTACACACCCTCTTTTAAGAAAG GAG
CTAAATTGTTACATAAAC
CTATTGTTTG G CAT G TTAACAAT G CAACTAATAAAG CC AC G TATAAAC CAAATACCTG
GTGTATACGTTGTCTTTGG AG CA
CAAAACCAGTTG AAACATCAAATTCGTTTG ATGTACTG AAG TC AG A G G AC G CG CA G G G AATG
G ATAATCTTG CCTG C G AA
G AT CTAAAACCAG TCT CTG AA G AAG TAG T G G AAAATCCTACCATACAG AAAG A C GTT CTTG
AG TG TAATG T G AAAACTAC
CG AAG TT GTAG GAG ACATTATACTTAAACCAG C AAATAATAGTTTAAAAATTA CAG AA G AG G TTG
G CCACACAG ATCTAA
TG G CTG CTTATG TAG ACAATTCTAG T CTTA CTATTAAG AAACCTAATG AATTAT CTAG A G
TATTAG GTTTGAAAACCCTTG C
TACTCATG GTTTAG CTG CTGTTAATAG TGTCCCTTG GG ATACTATAG CTAATTATG CTAAG C
CTTTTCTTAACAAAG TTG TT
AG TACAACTACTAACATAG TTACAC G GTGTTTAAACCGTGTTTGTACTAATTATATG
CCTTATTTCTTTACTTTATTG CTACA
ATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTAAAG CAT CTATG CCG ACTACTATAG CAAAG
AATACTG TTAAG AG
TGTCG G TAAATTTT G TCTAG AG G CTT CATTTAATTATTTG AAG T CACCTAATTTTT CTAAACT G
AT AAATATTATAATTT G GT
TTTTACTATTAAGTGTTTG CCTAG G TTCTTTAAT CTA CT CAACC G CTG CTTTAG
GTGTTTTAATGTCTAATTTAG GCATG CCT
TCTTACT G TACT G GTTAC AG AG AAG GCTATTTGAACTCTACTAATGTCACTATTG
CAACCTACTGTACTG G TT CTATACCTT
G TAG TG TTTG TCTTAGTG GTTTAGATTCTTTAG ACACCTATCCTTCTTTAG
AAACTATACAAATTACCATTTCATCTTTTAAAT
G G GATTTAACTG CTTTTG G CTTAGTTG CAG AGTG GTTTTTG G CATATATTCTTTTCACTAG
GTTTTTCTATGTACTTG GATTG
G CTG CAATCATG CAATTGTTTTTCAG CTATTTTG C AG TA CATTTTATTAG TAATTCTTG G
CTTATGTG GTTAATAATTAATCT
TGTACAAATG G CCCCG ATTTCAGCTATG GTTAGAATGTACATCTTCTTTG CAT CATTTTATTATGTATG
GAAAAGTTATGTG
CAT G TT G TAG AC G GTTGTAATTCATCAACTTGTATG AT G TG TTACAAAC G TAATAG A G
CAACAAG AG TC G AATG TAC AACT
ATTGTTAATG GTGTTAGAAGGTCCTTTTATGTCTATGCTAATG GAG GTAAAG G CTTTTG
CAAACTACACAATTG GAATTGT
GTTAATTGTG ATACATTCTGTG CT G G TAG TACATTTATTAG TG AT G AAG TTG C G AG AG
ACTTG T CA CTACAG TTTAAAAG A
CCAATAAAT C CTA CTG AC CAG T CTTCTTACATC G TTG ATAG TG TTACAG TG AA G AATG G
TT CCAT C CATCTTTACTTTG ATA
AAG CTG GTCAAAAG ACTTATG AAAG ACATTCTCT CTCTC ATTTTG TTAACTTAG AC AAC CT G AG
A G CTAATAAC A CTAAA G
GTTCATTG CCTATTAATGTTATAGTTTTTG ATGGTAAATCAAAATGTG AAGAATCATCTG C AAAATC AG CG
TCTGTTTACTA
CAGTCAG CTTAT G TG TCAAC CTATACT GTTACTAG ATC AG G CATTAGTGTCTGATGTTG
GTGATAGTG CG GAAGTTG CAGT
TAAAATGTTTG ATG CTTACG TTAATAC GTTTT CAT CAA CTTTTAAC G TA CC AATG G
AAAAACTCAAAACACTAGTTG CAACT
G CAGAAG CTGAACTTG CAAAGAATGTGTC CTTAGACAATGTCTTATCTACTTTTATTTCAGCAG CTCG G
CAAG G G TTTG TT
GATTCAG ATG TAG AAACTAAAG ATG TTG TTG AATG T CTTAAATTG TCA CATCAATCTG AC ATAG
AAG TTACTG G CGATAGT
TGTAATAACTATATG CTCACCTATAACAAAGTTGAAAACATG ACAC CC CG TG AC CTTG GTG CTTG
TATTG ACTG TAG TG CG
CGTCATATTAATG CG CAG G TAG CAAAAAGTCACAACATTG CTTTGATATG G AACGTTAAAG ATTTCATG
TCATTG T CTG AA
CAA CTAC G AAAAC AAATAC G TAG TG CTG CTAAAAAGAATAACTTACCTTTTAAGTTG ACATGTG C
AACTACTAG A CAAG TT
GTTAATG TTG TAA CAA CAAAG ATAG CACTTAAG G GTG GTAAAATTGTTAATAATTG GTTG AA G
CAGTTAATTAAAG TTA C A
CTTGTGTTCCTTTTTGTTG CTG CTATTTTCTATTTAATAACACCT G TT CATG TCAT G TCTAAACATACTG
ACTTTTCAAGTG AA
ATCATAG GATACAAG G CTATTGATG GTG GTGTCACTCGTGACATAG CATCTACAG ATACTTGTTTTG
CTAACAAACATG CT
GATTTTGACACATG GTTTAG CCAG CGTG GTG GTAGTTATACTAATGACAAAG CTTG CCCATTGATTG CT
G CAGTCATAACA
AG A G AAG TG G GTTTTGTCGTG CCTG GTTTG CCTG G CAC G ATATTAC G CAC AACTAATG
GTGACTTTTTG CATTTCTTACCTA
G AG TTTTTAG TG CAGTTG GTAACATCTGTTACACACCAT CAA AACTTATAG AG TA CA CTG ACTTTG
CAACATCAG CTTGTGT
TTTGG CTG CTG AATG TA CAATTTTTAAAG ATG CTTCTG GTAAG CC AG TAC CATATTG TTATG
ATACCAATG TA CTAG AAG GT
TCT G TT G CTTAT G AAAG TTTA C G C CCT G ACAC A CG TTATG T G CT CAT G GATG G
CTCTATTATTCAATTTCCTAACACCTACCT
TG AAGGTTCTGTTAG AG TG G TAA CAACTTTTG ATTCT G AG TACTG TAG G C AC G G C ACTT
G TG AAAG AT CA G AAG CTG GTG
TTTGT G TAT CTA CTA G TG G TAG AT G G G TACTTAACAAT G ATT ATTA CAG AT CTTTA
CCAG G AG TTTTCTG TG GTG TAG AT G C

TG TAAATTTACTTAC TAATATG TTTA CAC CACTAATTC AACCTATTG GTG CTTTG GACATATCAG
CATCTATAGTAG CTG GT
G GTATTGTAG CTATCG TAG TAA CATG CCTTG CCTACTATTTTATG AG GTTTAG AAG AG CTTTTGG
TG AATACAG TCATG TA
GTTG CCTTTAATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTG
GTGTTTATT
CTGTTATTTACTTGTACTTG ACATTTTATCTTACTAATG AT G TTTCTTTTTTAG CA CATATTCAG TG G
AT G GTTATGTTCACAC
CTTTAGTACCTTTCTG GATAACAATTG CTTATATCATTTG TATTTCCACAAAG
CATTTCTATTGGTTCTTTAGTAATTACCTAA
AG A G AC G T G TAG TC TTTAATG GTGTTTCCTTTAGTACTTTTG AAGAAG CTG CG CTGTG CA
CCTTTTTG TTAAATAAA G AAAT
GTATCTAAAGTTG CGTAGTGATGTG CTATTACCTCTTACG CAATATAATAG ATACTTAG CTCTTTATAATAAG
TACAAG TAT
TTTAGTG GAG CAATG GATACAACTAG CTA CAG AG AAG CTG CTTG TT G TC ATCTC G CAAAG G
CT CTCAATG ACTTCAGTAAC
TCAG GTTCTG ATGTTCTTTACCAACCACCACAAACCTCTATCACCTCAG CTGTTTTG CAG A G TG
GTTTTAGAAAAATG G CAT
TCCCATCTG GTAAAG TTG AG G GTTGTATGGTACAAGTAACTTG TG GTACAACTACACTTAACG GTCTTTG
G CTTGATG AC G
TAG TTTACTG TCCAA G ACAT G TG ATCTG CAC CT CT G AAG A CATG CTTAACCCTAATTATG AA
G ATTTACT CATTC G TAA G TC
TAATCATAATTTCTTG G TA CAG G CTG G TAAT G TT CAACT CAG G GTTATTG
GACATTCTATGCAAAATTGTG TACTTAAG CTT
AAG GTTG ATACAG CCAAT CCTAAG ACAC CTAAG TATAAG TTT G TTC G CATT CAACC AG G AC
AG A CTTTTT CAG TG TTA G CT
TGTTACAATG G TTCACCATCTGGTGTTTACCAATGTG CTATG AG G CCCAATTTCACTATTAAG
GGTTCATTCCTTAATG G TT
CAT G TG G TAG TG TTG GTTTTAACATAGATTATG ACTGTGTCTCTTTTTGTTACATG CACCATATG
GAATTACCAACTGG AG T
TCATG CT G G C ACAG A CTTA G AAG GTAACTTTTATGG ACCTTTTG TTG A CAG G CAAACAG
CACAAG CAG CTG G TAC G G AC A
CAACTATTACAGTTAATGTTTTAG CTTG GTTGTACG CTG CTGTTATAAATG G A G ACAG GTG
GTTTCTCAATCG ATTTACCAC
AACTCTTAATG ACTTTAACCTTGTG G CTATG AAGTACAATTATG AACCTCTAACACAAG ACCATGTTG
ACATACTAG G AC CT
CTTTCTG CT CAAACTG G AATT G CC GTTTTAG ATATGTGTG CTTCATTAAAAGAATTACTG CAAAATG
GTATGAATGG AC GT
ACC ATATT G G GTAGTG CTTTATTAGAAG ATG AATTTACACCTTTTGATGTTGTTAG ACAATG CTC AG
G T G TTA CTTT CCAAA
GTG CAGTGAAAAGAACAATCAAG G G TA CA CACCA CTG G TTG TTACTCACA ATTTTG
ACTTCACTTTTAG TTTTA G TCC AG A
GTACTCAATG G T CTTTG TT CTTTTTTTTG TATG AAAATG CCTTTTTACCTTTTG CTATG G
GTATTATTG CTATGTCTGCTTTTG
CAATG AT GTTTG TC AAACATAAG C ATG CATTTCTCTGTTTGTTTTTGTTACCTTCTCTTG C CACT G
TA G CTTATTTTAATATG G
TCTATATG CCTG CTAGTTGG G TG AT G C G TATTATG AC ATG GTTG
GATATGGTTGATACTAGTTTGTCTG GTTTTAAG CTAA
AAG ACTGTGTTATGTATG CATCAG CTG TAG TG TTACTAATCCTTATG ACAG CAA G AACTG TG TATG
ATG ATG GTG CTAG GA
G AG TG T G G AC ACTTATG AATG TCTT G ACACT CG TTTATAAAG TTTATTATG GTAATG CTTTA
G AT CAA G CC ATTTCCAT G TG
G G CTCTTATAATCTCTGTTACTTCTAACTACTCAG GTG TAG TTACAA CTG TC ATG TTTTTG G CCAG
AG GTATTGTTTTTATGT
GTGTTGAGTATTG CCCTATTITCTTCATAACTGGTAATACACTICAGTGTATAATG CTAGTTTATTGTTTCTTAG
G CTATTTTT
GTACTTGTTACTTTG GCCTCTTTTGTTTACTCAACCG CTACTTTAG ACTG ACTCTTG
GTGTTTATGATTACTTAGTTTCTACAC
AG G AG TTTAG ATATATG AATTC AC AG G G A CTACTCCC ACC CAA G AATAG CATAGATG
CCTTCAAACTCAACATTAAATTGT
TG G GTGTTG GTG G C AAACCTTG TATCAAAG TAG CCACTGTA CAG TCTAAAATG TCAG ATGTAAAG
TG CACAT CAG TAG TC
TTACTCTCAGTTTTG CAACAACTCAG AGTAGAATCATCATCTAAATTGTG G G
CTCAATGTGTCCAGTTACACAATGACATTC
TCTTAG CTAAAG ATACTACTG AAG CCTTTG AAAAAATGGTTTCACTACTTTCTGTTTTG CTTTCCATG C
AG G GTG CTGTAG A
CATAAACAAG CTTTG TG AA G AAAT G CT G G A CAACA G GG CAACCTTACAAG CTATAG CCTCAG
AG TTTAG TTCC CTTCC ATC
ATATG CA G CTTTTG CTACTG CTCAAGAAG CTTATG AG CAG G CTGTTGCTAATGGTG ATTC TG AA
G TTG TTCTTAAAAAG TT
G AA G AAG TCTTTG AATG TG G CTAAATCTGAATTTG ACC G TG AT G CAG CCATG
CAACGTAAGTTG GAAAAGATG G CT G ATC
AAG CTATGACCCAAATGTATAAACAG G CTA G ATCTG AG G AC AAG AG G G CAAAAGTTACTAGTG
CTATGCAG ACAATG CTT
TT CACTATG CTTAG AAAG TT G GATAATG ATG CACTCAACAACATTATCAACAATG CAA G AG AT G
GTTGTGTTCCCTTGAAC
ATAATACCTCTTACAACAGCAG CCAAACTAATG GTTGTCATACCAGACTATAACACATATAAAAATACGTGTG
ATG GTACA
ACATTTACTTATG CAT CAG CATTGTG G G AAATCCAACAG GTTGTAG ATG
CAGATAGTAAAATTGTTCAACTTAGTG AAATT
AG TATG GACAATTCACCTAATTTAG CATG G CCTCTTATTGTAACAG CTTTAAG G G
CCAATTCTGCTGTCAAATTACAG AATA
ATG AG CTTAG TCCTG TTG CACTACGACAGATGTCTTGTG CTG CCG G TACTA CAC AAA CTG CTTG
CACTG ATG AC AATG CGT
TAG CTTACTACAACACAACAAAGG GAG G TAG GTTTGTACTTG CACTG TTAT CC G ATTTAC AG
GATTTGAAATG G G CTAG AT
TCCCTAAG AG TG ATG G AACTG GTACTATCTATACAG AACTG G AACC ACCTT G TAG G TTTG
TTACAG AC ACACCTAAAG G TC
CTAAAGTGAAGTATTTATACTTTATTAAAG G ATTAA ACAACCTAAATA G AG GTATG GTACTTG G TAG
TTTAG CTG CCACAG
TACGTCTACAAG CTG G TAATG C AAC AG AAG TG CCTG CC AATTC AACTG TATTATCTTTCT GT G
CTTTTG CT G TAG ATG CTG C
TAAAGCTTACAAAGATTATCTAG CTAGTG G G G GACAACCAATCACTAATTGTGTTAAG ATG TTG TG TA
CACACA CTG GTAC
TG GTCAG G CAATAAC AG TTACACC G GAAG CCAATATG G ATCAAGAATCCTTTG GTG GTG CAT C
GT G TTG TCT G TACTG CC
GTTG CCACATAGATCATCCAAATCCTAAAG GATTTTGTG ACTTAAAAG GTAAG TATG TA CAAATACCTA
CAA CTTG TG CTA
ATG ACCCTGTGG GTTTTACACTTAAAAACACAGTCTGTACCG TCTG CG GTATGTG GAAAG GTTATGG CTG
TAG TTG TG ATC
AACTCCG CGAACCCATGCTTCAGTCAG CTGATG CACAATCGITTITAAACG G GITTG CG GTG TAAG TG
CA G CCCGTCTTAC
ACC GTG CGG CACAG G CACTAGTACTG ATGTCGTATACAG G G CTTTTG ACAT CTAC AATG AT
AAAG TAG CTG GTTTTG CTAA
ATTCCTAAAAACTAATTGTTG TCG CTTCCAAGAAAAG G AC G AAG ATG AC AATTTAATTG
ATTCTTACTTT G TAG TTAA G AG
ACACACTTTCTCTAACTACCAACATG AAGAAACAATTTATAATTTACTTAAG G ATTGTCCAG CTG TT G
CTAAAC ATG A CTTC
TTTAAG TTTAG AATAG AC G GTG ACATG GTACCACATATATCACGTCAACGTCTTACTAAATACACAATG G
CA G A CCTC GTC

TAT G CTTTAAG G CATTTT GAT G AAG G TAATTGT G ACACATTAAAAG AAATACTTGTC
ACATACAATTG TTGT G ATG ATG AT
TATTTCAATAAAAAG G ACTGGTATG ATTTTGTAGAAAACCCAG ATATATTACGCGTATACG CC AAC TTAG
GT G AACGTGTA
CG CCAAG CTTTGTTAAAAACAGTACAATTCTGTGATG CCATG CGAAATG CTG GTATTGTTG GTGTACTG
AC ATTAG ATAAT
CAA G ATCT CAAT G GTAACTG GTATGATTTCG GTG ATTTC ATACAAACC AC G CCAG GTAGTG
GAGTTCCTGTTGTAGATTCT
TATTATTCATTGTTAATG CCTATATTAACCTTG ACCAG GG CTTTAACTG C AG AGT CACATGTTG
ACACTG ACTTAACAAAG C
CTTACATTAAGTG G G ATTTGTTAAAATATGACTTCACG G AAG AG AG GTTAAAACTCTTTG
ACCGTTATTTTAAATATTGG G
ATC AG ACATACCA CCCAAATTGT GTTAACTG TTTG G ATG ACAG ATG CATTCTG CATTGTG
CAAACTTTAATGTTTTATTCTC
TACAGTGTTCCCACTTACAAGTTTTG G ACCACTAGTG AG AAAAATATTTGTTGATG
GTGTTCCATTTGTAGTTTCAACTG GA
TAC C ACTT CAG AG AG CTAG GT GTTG TACATAATCAG G ATG TAAACTTACATAG CT CTAG
ACTTA GTTTTAAG GAATTACTT
GTGTATG CTG CTG ACCCTG CTATG CAC G CTG CTTCTG GTAATCTATTACTAGATAAACG CACTACGTG
CTTTTCAGTAG CTG
CA CTTACTAACAATGTTG CTTTTCAAACTGTCAAACCCG GTAATTTTAACAAAG ACTT CTATG ACTTTG
CTGTGTCTAAG GG
TTTCTTTAAG G AAG G AAGTTCTGTTG AATTAAAACACTTCTTCTTTG CT CAG G ATG GTAATG CTG
CTATCAG CG ATTATG AC
TACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTG
ATT
GTTACG ATG GTG G CTGTATTAATG CTAACCAAGTCATCGTCAACAACCTAGACAAATCAG CTG
GTTTTCCATTTAATAAAT
G G G GTAAG G CTAG ACTTTATTATG ATTC AAT G AG TTATG AG GATCAAGATG CA CTTTTC
GCATATACAAAACG TAATGTCA
TCCCTACTATAACTCAAATGAATCTTAAGTATG CCATTAGTG CAAAG AATAG AG CTCG CA CC GTAG CTG
GTGTCTCTATCT
GTAGTACTATG ACCAATAGACAGTTTCATCAAAAATTATTG AAATCAATAG CCG CCACTAG AG
GAGCTACTGTAGTAATTG
G AA CAAG CAAATTCTATG GTG GTTG G CA CAACATGTTAAAAACTGTTTATAG TG ATGTAGAAAAC
CCTCACCTTATG G GTT
G G GATTATCCTAAATGTG ATAG A G CCATG CCTAACATG CTTAG AATTATG G C CTCACTTG
TTCTTG CT CG CAAACATACAA
CG TGTTG TAG CTTGTCACACCGTTTCTATAGATTAG CTAATG AG TGTG
CTCAAGTATTGAGTGAAATGGTCATGTGTG G CG
GTTCACTATATGTTAAACCAG GTG G AAC CTCATCAG G AG AT G CCACAACTGCTTATG
CTAATAGTGTTTTTAACATTTGTCA
AG CTGT CACG G CCAATGTTAATGCACTTTTATCTACTGATG GTAACAAAATTG CC G ATAA GTAT GTC
CG CAATTTA C AAC A
CAG ACTTTATG AG TG T CTCTATAG AAATA G AGAT GTT GACA CA G AC TTTGTG AATG AG
TTTTACG CATATTTG CGTAAACA
TTTCTC AAT G ATGATACT CT CTG ACG AT G CT GTTG TGT GTTTCAATAG CACTTATG CAT
CTCAA G GT CTAGTG G CTAG CATA
AAG AA CTTTAAG TCAG TTCTTTATTATC AAAACAATGTTTTTATGTCTG AAG CAAAATGTTG G ACT G
AG A CTG A CCTTACTA
AAG GACCTCATG AATTTTG CTCTCAACATACAATG CTAGTTAAACAG G GTGATG
ATTATGTGTACCTTCCTTACCCAG ATCC
ATCAAGAATCCTAG G G G CCG G CTGTTTTGTAG ATGATATCGTAAAAACAGATG
GTACACTTATGATTGAACG GTTCGTGT
CTTTAG CTATAG AT G CTTACC CA CTTA CTAAA CATCCTAAT CAG G AGTATG CT G AT
GTCTTTCATTT GTACTTAC AATACATA
AGAAAG CTACATGATG AGTTAACAG G ACAC ATGTTAG A CATG TATT CTGTTATG
CTTACTAATGATAACACTTCAAG GTAT
TG G G AA CCTG A GTTTTAT G AG G CTATGTACACACCG CATACAGTCTTACAG G CTGTTG G G G
CTT GT G TTCTTT G CAATTCA
CAG ACTT C ATTAA G ATG TG GTG CTTGCATACGTAGACCATTCTTATGTTGTAAATG
CTGTTACGACCATGTCATATCAACAT
CAC ATAAATTAGT CTTG TCT G TTAATCCG TATG TTTG CAATG CTCCAG G TTG TG AT GTCA CAG
AT GTG ACTCAACTTTACTT
AG G AG GTATG AG CTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTG CTAATG
GACAAGTTTTTG GTTTA
TATAAAAATACATGTGTTG GTAGCG ATAATGTTACTG ACTTTAATG CAATTG CAACATGTGACTG G
ACAAATG CT G G TG AT
TAC ATTTTAG CTAACACCTG TACT G AAAG ACTCAAG CTTTTTG C AG CAGAAACG CTCAAAG
CTACTG AG G AG ACATTTAAA
CT GT CTTAT G GTATTG CTACTGTACGTGAAGTG CTG TCTGACAG AG AATTACAT CTTTC ATG G
GAAGTTG GTAAA CCTAG A
CCACCACTTAACCGAAATTATGTCTTTACTG GTTATCG TGTAACTAAAAACAG TAAAGTACAAATAG G AG AG
TAC A CCTTT
GAAAAAG GTGACTATG GTG ATG CTGTTGTTTACC G AG G TACAACAACTTACAAATTAAATGTTG
GTGATTATTTTGTG CTG
ACATCAC ATA CA G TAATG CCATTAAGTG CACCTACACTAGTG CCACAAG AG
CACTATGTTAGAATTACTG G CTTATACCCA
ACA CTCAATATCTCAGATG AG TTTTCTAG CAATGTTG CAAATTATCAAAAG GTTG GTATG CAAAAG
TATTCTAC ACT CCAG
G GACCACCTG G TACT G GTAAGAGTCATTTTG CTATTG G CCTAG CTCTCTACTACCCTTCTG CTCG
CATAGTGTATACAG CTT
G CTCTCATG C CG CT GTTG ATG CACTATGTG AG AA G G CATTAAAATATTTGCCTATAG ATAAAT G
TA GTAG AATTATAC CTG
CAC GTG CTCG TGTAG AGT GTTTTG ATAAATTCAAAGTGAATTC AACATTAG AAC AGTATGTCTTTTGTA
CT GTAAATG CATT
G CCTG AG ACGACAG CAGATATAGTTGTCTTTG ATGAAATTTCAATG G CCACAAATTATGATTTG
AGTGTTGTCAATG CCAG
ATTACGTG CTAAG CAC TATG TGTA CATTG G CG AC CCTGCTC AATTACCTG CACCACG CACATTG
CTAACTAAG G G CAC ACT
AGAACCAG AATATTTCAATTCAGTGTGTAG ACTTATGAAAACTATAGGTCCAG ACATGTTCCTCGG
AACTTGTCG G CGTTG
TCCTG CTG AAATTGTTG AC ACTG TG AG TG CTTT G GTTTATG ATAATAAG CTTAAAG
CACATAAAGA C AAATC AG CT CAATG
CTTTAAAATGTTTTATAAG G GTGTTATCACG CATG ATG TTTC AT CTG CAATTAAC AG GC
CACAAATAG G CGTG GTAAG AGA
ATTCCTTACACGTAACCCTG CTTG GAG AAAAG CT GTCTTTATTT CAC CTTATAATT CACAG AATG
CTGTAG CCTCAAAG ATT
TTG G GACTACCAACTCAAACTGTTGATTCATCACAG G GCTCAGAATATG
ACTATGTCATATTCACTCAAACCACTG AAACA
G CTCA CT CTTGTAAT GTA AA CA G ATTT AATGTTG CTATTA C CA G A G CA AAA GTA G
GCATACTTTG CATA ATGT CTG ATA G A
G ACCTTTATG ACAAGTTG CAATTTACAAGTCTTGAAATTCCACGTAG G AATGTG G CAACTTTACAAG
CTGAAAATGTAACA
G GACTCTTTAAAG ATTGTAGTAAG GTAATCACTG G G TTA C ATCCTACAC AG G C AC CTA
CACACCTC AG TGTTG AC ACTAAA
TT CAAAA CTG AAG GTTTATGTGTTGACATACCTG G CATACCTAAG G ACATGACCTATAG
AAGACTCATCTCTATGATG G GT
TTTAAAATGAATTATCAAGTTAATG GTTACCCTAACATGTTTATCACCCG CGAAGAAG CTATAAG
ACATGTACGTG CATGG

AUG GCTTCG ATGTCG AG G G GTGTCATG CTACTAG AG AAG CTGTTG G TACCAATTTACCTTTACAG
CTAG G TTTTTCTA CA
G G TG TTAACCTAG TT G CTG TACCTACAG GTTAT G TT G ATAC ACCTAATAATA CAG ATTTTT
CCAG AGTTAGTG CTAAACCAC
CG CCTG G AG ATCAATTTAAACACCT CATACCA CTTATG TAC AAAG G ACTTCCTTG
GAATGTAGTGCGTATAAAG ATTGTAC
AAATGTTAAGTG ACACACTTAAAAATCTCTCTG ACAG AG TCG TATTTG T CTTAT G G G CACATG G
CTTTG A G TTG ACATCTAT
GAAGTATTTTGTG AAAATAG G ACCTG AG CGCACCTGTTGTCTATGTG ATAGACGTG CCACATG CTTTTC
CACTG CTTCAG A
CACTTATG CCTGTTG G CATCATTCTATTG G ATTTG ATTACGTCTATAATCCGTTTATG
ATTGATGTTCAACAATG G G GTTTTA
CAG GTAACCTACAAAG CAACCATGATCTGTATTG TCAAGTCCATG GTAATG CACATG TAG
CTAGTTGTGATG CAATC ATG A
CTAG GTGTCT AG CTGTCCACGAGTG CTTTGTTAAGCGTGTTGACTG GACTATTGAATATCCTATAATTG G
TG ATG AACTG A
AG ATTAATG CG G CTTGTAGAAAG GTTCAACACATG GTTGTTAAAG CTG CATTATTAG C AG
ACAAATTCCCAGTT CTTC AC G
ACATTG G TAACCCTAA AG CTATTAAGTGTGTACCTCAAG CT G ATG TAG AATG G AAG TT CTATG
AT G CAC AG CCTTG TAG TG
ACAAAG CTTATAAAATAG AAGAATTATTCTATTCTTATG CCACAC ATTCTG AC AAATT CACAG ATG
GTGTATGC CTATTTTG
GAATTG C AATGT C G ATAG ATATCCT G CTAATTCCATTG TTTG TAG ATTTG A CACTA G AG T G
CTATCTAACCTTAACTTG CCT
G G TTG TG AT G GTG G CAG TTT G TAT G TAAATAAAC ATG C ATTCC ACA CAC CAG
CTTTTGATAAAAGTG CTTTTGTTAATTTAA
AACAATTACCATTTTTCTATTACTCTGACAGTCCATGTGAGTCTCATG
GAAAACAAGTAGTGTCAGATATAGATTATGTACC
ACTAAAGTCTG CTACG TGTATAACACGTTG CAATTTAG GTG GTG CTGTCTG TAG AC ATCATG CTAATG
AG TACAG ATTG TA
TCTCGATG CTTATAACATG ATG ATCTC AG CTG G CTTTAG CTTGTG GGTTTACAAACAATTTG
ATACTTAT AAC CT CTG G AAC
ACTTTTACAAG A CTTC AG AG TTTA G AAAATG TG G CTTTTAATGTTGTAAATAAG G
GACACTTTGATG GACAACAG G GTG A
AG TACCAG TTT CTATCATTAATAACACTG TTTACA CAAAAG TTG ATG G TG TT G ATG TAG AATTG
TTTG AAAATAAAACAAC
ATTACCTG TTAATG TAG CATTTG AG CTTTG GG CTAAG CG CAACATTAAAC C AGTA CC AG AG
GTG AAAATACTCAATAATTT
G G GTG TG G ACATTG CTG CTAATACTG TG AT CTG G G ACTACAAAAG AG ATG CTCCAG
CACATATATCTACTATTG GTGTTTG
TT CTATG ACTG ACATAG CCAAGAAACCAACTGAAACG ATTTGTG CA CCACTCACT GTCTTTTTTG ATG
G TAG AG TTG ATG G
TCAAGTAGACTTATTTAG AAATG CCCGTAATGGTGTTCTTATTACAGAAG GTAGTGTTAAAG G TTTA
CAACCATCTG TAG G
TCC CAAACAAG CT AG TCTTAATG GAGTCACATTAATTG G AG AA G CC G TAAAAA CACAG TTC
AATTATTATAAG AAAG TTG A
TG GTGTTGTCCAACAATTACCTG AAACTTACTTTACTC AG AG TAG AAATTTACAAGAATTTAAACCCAG G
AG TCAAATG G A
AATTGATTTCTTAG AATT AG CTATG G AT G AATT CATTG AACG GTATAAATTAG AAGG CTAT G C
CTTC G AA CATAT C G TTTAT
G G AG ATTTTA GTCATAGTC AG TTAG GTG GTTTACATCTACTGATTG GACTAG CTAAACGTTTTAAG G
AATCACCTTTTG AA
TTAG AAG ATTTTATTCCTATG GACAG TACAG TTAAAAA CTATTTCAT AAC AG ATG C G CAAACAG
GTTCATCTAAGTGTGTG
TGTTCTGTTATTG ATTTATTACTTG ATG ATTTTG TT G AAATAATAAAATCC CAAG ATTTATCTG TAG
TTTCTAA G G TTG T CAA
AGTGACTATTG ACTATACAGAAATTTCATTTATG CTTTG GTGTAAAGATG G CCATG TAG AAAC
ATTTTACC CAAAATTACAA
TCTAGTCAAG CGTGG CAACCG G GTGTTG CTATG CCTAATCTTTACAAAATG
CAAAGAATGCTATTAGAAAAGTGTG AC CTT
CAAAATTATG GTGATAGTG CAACATTAC CTAAAG G CATAATG ATGAATGTCG
CAAAATATACTCAACTGTGTCAATATTTA
AACACATTAACATTAG CT G TAC CCTATAATAT G AG AG TTATA CATTTTG GTG CTGGTTCTGATAAAG
G A G TTG CACC AG GT
ACAG CTG TTTTAAG A C AG T G G TTG CCTACG G G TA C G CT G CTT G TC G ATT CAG AT
CTTAAT G ACTTTG TCT CTG ATG CA G ATT
CAA CTTTG ATTG GTGATTGTG CAACTGTACATACAG CTAATAAATG GGATCTCATTATTAGTGATATGTACG
ACCCTAAG A
CTAAAAATGTTACAAAAG AAAAT G ACT CTAAA G AG G GTTTTTTCACTTACATTTGTG G
GTTTATACAACAAAAG CTAG CTC
TT G GAG GTTCCGTG G CTATAAAG ATAACAGAACATTCTTG G AATG CT G ATCTTTATAAG CTCATG
G GACACTTCG CAT G GT
G GACAG CCTTTGTTACTAATGTGAATG CGTCATCATCTG AAG CATTTTTAATTG GATGTAATTATCTTG G
CAAAC CAC G CG
AACAAATAG ATG GTTATGTCATG CATG CAAATTACATATTTTG G AG G AATACAAATCC AATTC AG TT
G T CTTCC TATT CTTT
ATTTG AC ATG AG TAAATTTC CCCTTAAATTAAG G G G TA CTG CTGTTATGTCTTTAAAAG AAG
GTCAAATCAATG ATATGATT
TTATCTCTTCTTAGTAAAG G TAG A CTTATAATTAG AG AAAACAA CAG AG TT G TTATTTCTA G TG
ATGTTCTT G TTAACAACT
AAACGAACAATGTTTGTTTTTCTTGTTTTATTG
CCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAGAACTCAATTACC
CCCTG CATACACTAATTCTTTCACACGTG GTGTTTATTACCCTGACAAAGTTTTCAG ATCCT CAG TTTTAC
ATT CAA CTCA G G
ACTTGTTCTTACCTTTCTTTTCCAATGTTACTTG GTTCCATG CTATACATGTCTCTG G G ACCAATG
GTACTAAG AG GTTTG AT
AACCCTG TCCTACCATTTAATGATG GTGTTTATTTTG CTTCCA CTG A G AAG TCTAACATAATAA G AG
G CTG G ATTTTTG G TA
CTA CTTTAG ATTC G AAG ACC CAG T CCCTA CTTATTG TTAATAAC G
CTACTAATGTTGTTATTAAAGTCTGTGAATTTCAATTT
TGTAATG ATCCATTTTTG G GTGTTTATTACCACAAAAACAACAAAAGTTG GATG GAAAGTG AGTTCAG A G
TTTATTCTAG T
G CGAATAATTGCACTTTTGAATATGTCTCTCAG CCTTTTCTTATG G ACCTTG AAG GAAAACAG G
GTAATTTCAAAAATCTTA
G G GAATTTGTGTTTAAGAATATTGATG GTTATTTTAAAATATATTCTAAG CACACG CCTATTAATTT AG TG
CGTGATCTCCC
TCAG GGTTTTTCG G CTTTAG AA CCATT G G TAG ATTT G CC AATAG GTATTAACATCACTAG
GTTTCAAACTTTACTTG CTTTA
CATAGAAGTTATTTG ACTCCTG GTGATTCTTCTTCAG GTTG G AC AG CTG GTG CTG CAG
CTTATTATGTG G GTTATCTTCAAC
CTAG GACTTTT CTATTAAAATATAATG AAA ATG G AACCATTA CA G ATG CTG TAG ACTGTG CA
CTTG ACCCTCTCTCAG AA A
CAAAGTG TAC G TTG AAATCCTTCA CTG TAG AAAAAG G AATCTATCAAACTT CTAACTTTA G AG
KCCAACCAACAG AATCTA
TTGTTAGATTTCCTAATATTACAAACTTG TG C CCTTTTG G TGAAGTTTTTAACG CCACCAGATTTG CAT
CTG TTTAT G CTTG G
AAC AG G AA G AG AATCAG CAACTGTGTTG CTGATTATTCTGTCCTATATAATTCC G CAT
CATTTTCCACTTTTAAG TG TTATG
G AG TG T CTCCTACTAAATTAAATG AT CTCT G CTTTACTAATG T CTATG CAG ATTC ATTTG
TAATTA G AG G TG AT G AAG TCAG

ACAAATCGCTCCAG G G CAAACTG GAAAG ATTG CTG ATTATAATTAT AAATTACCAG ATG ATTTTAC
AG GCTG CGTTATAG C
TT G GAATTCTAACAATCTTG ATTCTAAG GTTG GTG GTAATTATAATTACCTGTATAG ATT G TTT AG
GAAGTCTAATCTCAAA
CCTTTTG AG AG AG ATATTT CAACTG AAAT CTAT CAG G CCG GTAG CACACCTTGTAATG
GTGTTGAAG GTTTTAATTGTTAC
TTTCCTTTACAATCATATG GTTTCCAACCCACTAATG GTGTTG G TTACC AAC CATACAG AG TAG TAG
TACTTTCTTTTG AACT
TCTACATG CACCAG CAACTGTTTGTG GACCTAAAAAGTCTACTAATTTG
GTTAAAAACAAATGTGTCAATTTCAACTTCAAT
G GTTTAACAG G CACAG GTGTTCTTACTG AG TCTA ACAAAAAG TTTCTG CCTTTCCAACAATTTGG CAG
AG AC ATTG CTG AC
ACTACTG ATG CT G TC CG TG ATCCA CAG AC ACTT G AG ATTCTT G AC ATTACA CCATG
TTCTTTTG GTG GTGTCAGTGTTATAA
CAC CAG G AACAAATACTTCTAACCAG GTTG CTGTTCTTTATCAG G GTGTTAACTG CA CAG
AAGTCCCTGTTG CTATTCATG C
AG ATCAACTTACTCCTA CTTG GCGTGTTTATTCTACAG GTTCTAATGTTTTTCAAACACGTG CAG
GCTGTTTAATAG GG G CT
G AA CATG TCAACAA CTCAT ATG AG TG T G ACATACCCATTG GTG CAG GTATATG CG
CTAGTTATCAGACTCAGACTAATTCT
CCTCG G CGG G CAC GTAG TG TAG CTAGTCAATCCATCATTG CCTACACTATGTCACTTG GTG CAG
AAAATTCAGTTG CTTAC
TCT RATAACTCTATTG CCATACCCACAAATTTTACTATTAG T G TTA CCACA G AAATTCTAC CA G TG
TCTATG A CCAAG ACATC
AG TAG ATTG TACAATG TACATTTG TG GTGATTCAACTGAATG CAG CAATCTTTTG TT G CAATATG G
CAGTTTTTGTACACAA
TTAAACC GTG CTTTAACTG GAATAG CT G TT G AACAA G ACAAAAACAC CC AAG AAGTTTTTG
CACAAGTCAAACAAATTTAC
AAAACACCACCAATTAAAG ATTTTG GTG GTTTTAATTTTTCACAAATATTACCAGATCCATCAAAACCAAG
CAAG AG GTCAT
TTATTG AAG AT CTACTTTT CAACAAAG TG A CACTTG C AG ATG CTG G CTTCATCAAACAATATG
GTGATTG CCTTG GTG ATAT
TG CTG CTAG AG AC CTCATTTG TG CACAAAAG TTTAACGG CCTTACTGTTTTG CCACCTTTG CTCA
CAG AT G AAAT G ATT G CT
CAATACACTTCTGCACTGTTAGCG G GTACAATCACTTCTGGTTG G ACCTTTG GTG CAG GT G CT G
CATTACAAATACCATTT
G CTATG CAAATG G CTTATAG GTTTAATG GTATTG G AG TTA CACA G AATG TTCTCTAT G AG
AACCAAAAATTG ATTG CCAAC
CAATTTAATAGTG CTATTGG CAAAATTCAAG ACTCACTTTCTTCCACAG CAAGTGCACTTGG
AAAACTTCAAGATGTG GTC
AACCAAAATG CAC AAG CTTTAAACACG CTTGTTAAACAACTTAG CTCCAATTTTG GTG
CAATTTCAAGTGTTTTAAATGATA
TCCTTT CAC G T CTTG ACAAAG TTG AG G CTGAAGTGCAAATTGATAG G TT G ATC ACAG G
CAGACTTCAAAGTTTG CA G ACAT
ATGTGACTCAACAATTAATTAG AG CT G CAG AAATC AG AG TTTCTG CTAATCTTG CTG CTACTAAAAT
G TC AG AGT G TG TAC
TT G G ACAATCAAAAAG AG TTG ATTTTTG TG G AAAG GG C TATCATCTTATG T CCTTC CCTC AG
TCA G CACCTCATG G T G TAG
TCTTCTTG C AT G TG ACTTATGTCCCTG CACAAGAAAAG AACTTCACAACTG CTCCTG CCATTTG
TCATGATGG AAAAG CA CA
CTTTCCTCGTGAAG GTGTCTTTGTTTCAAATG G CACACACTG GTTTGTAACACAAAG
GAATTTTTATGAACCACAAATCATT
ACTACAGACAACACATTTGTGTCTG GTAACTGTG ATGTTGTAATAG
GAATTGTCAACAACACAGTTTATGATCCTTTG CAA
CCTG AATTAG ACT CATTCAAG GAG G AG TTAG ATAAATATTTTAAG A ATCATACATCACCAG ATG TT
G ATTTAG GTG ACATC
TCTG G CATTAATG CTTCAGTTGTAAACATTCAAAAAGAAATTG ACCG CCTCAATG AG GTTG
CCAAGAATTTAAATGAATCT
CTCATCG ATCTCCAAGAACTTG G AAAG TATG AG CAGTATATAAAATG GCCATG GTACATTTG G CTAG
GTTTTATAG CT G G C
TTGATTG CCATAGTAATG G TGACAATTATG CTTTG CTG TATG AC CAG TTG CTGTAGTTGTCTCAAG G
G CTGTTGTTCTTGTG
G AT CCTG CTG CAAATTTG AT G AAG ACGACTCTG AG CC AG TG CTCAAAG G A G TCAAATTAC
ATTAC AC ATAAAC G AACTTAT
G G ATTTG TTTAT G AG AATCTT CACAATTG G AACTG TAACTTTG AA G CAAG GTG AAATCAAG G
AT G CTACTCCTTCAG ATTT
TGTTCG CG CTACTG CAACG ATACCG ATACAAG CCTCACTCCCTTTCG GATG G CTTATTGTTG G
CGTTG CACTTCTTG CTG TT
TTTCAG AG CG CTTCCAAAATCATAACCCTCAAAAAG AG ATG G CAACTAG CACTCTCCAAG G
GTGTTCACTTTGTTTGCAAC
TTG CTGTTGTTGTTTG TAACAGTTTACTC AC ACCTTTTG CTCGTTG CTG CTG G CCTTGAAG
CCCCTTTTCTCTATCTTTATG CT
TTAGTCTACTTCTTG CAG AGTATAAACTTTG TAAG AATAATAATG AG G CTTTG G CTTTG CTG
GAAATG CCGTTCCAAAAAC
CCATTACTTTATGATG CCAACTATTTTCTTTG CTGG
CATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTC
TT CAATTG TCATTACTTCAG GTG ATG G CAC AAC AAG TCC TATTTCTG AAC AT G
ACTACCAGATTG GTG GTTATACTG AAAA
ATG G GAATCTG G AG TAAAAG ACTG TG TT G TATTACAC AG TTACTT CACTTCAG ACTATTA
CCAG CTGTACTCAACTCAATTG
AG TACAG ACACTG GTGTTG AACATGTTACCTTCTTC ATCTACAATAAAATT GTTGATG AG CCTGAAG AA
CATGTCCAAATT
CAC ACAATC G ACG GTTCATCCG GAG TTG TTAATCCAG TAATG G AACCAATTTATG ATG AACCG
ACGACGACTACTAG CGT
G CCTTTGTAAG CACAAG CTG ATG AG TAC G AACTTATGTACT CATTCGTTTCG G AAG AG M CAG
GTACGTTAATAGTTAATA
G CGTACTTCTTTTTCTTGCTTTCGTG GTATTCTTG CTAGTTACACTAG CCATCCTTACTG CG
CTTCGATTGTGTG CGTACTG C
TG CAATATTG TTAACG TG A G TCTTG TAAAACCTTCTTTTTACG TTTACTCT CG TG TT AAAAAT
CTG AATTCTTCTAG AG TTCC
TG ATCTTCTGGTCTAAACGAACTAAATATTATATTAGTTTTTCTGTTTG G AA CTTTAATTTTAG CCATG G
CAG ATTCCAACG
GTACTATTACCGTTG AAG A G CTTAAAAAG CT CCTTG AAC AATG GAACCTAGTAATAG
GTTTCCTATTCCTTACATGG ATTTG
TCTTCTACAATTTG CCTATG CCAACAG GAATAG GTTTTTGTATATAATTAAGTTAATTTTCCTCTG G
CTGTTATG G CCAGTAA
CTTTAG CTTGTTTTGTG CTTG CT G CT GTTTACA G AATAAATTG GATCACCG GTG GAATTG CTATCG
CAATG G CTTGTCTTGT
AGG CTTGATGTG G CTCAG CTACTTCATTG CTTCTTTCAG ACTGTTTG CG C GTACGCGTTCCATGTG
GTC ATTC AATCCA G AA
A CTAA CATTCTT CTCAACGTG CCA CTCCATG G CACTATTCTGACCAG ACC G CTTCTAG AAAG TGAA
CTCGTAATC GG AG CT
GTGATCCTTCGTG GACATCTTCGTATTGCTGG ACACCATCTAG G AC G CTG TG AC ATC AAG G AC
CTG CCTAAAGAAATCACT
GTTG CTACATCACGAATG CTTTCTTATTACAAATTG G GAG CTTCG CAG CGTGTAG CAG GTGACTCAG
GTTTTG CTG CATAC
AGTCGCTACAG GATTG G CAA CTATAAATTAAACA CAG ACCATTC CAGTAG CAGTGACAATATTG CTTTG
CTTGTACAGTAA
GTG ACAACAG ATGTTTCATCTCGTTG ACTTTCAGGTTACTATAG C AG A G ATATTA CTAATTATTATG
AG G ACTTTTAAA G TT

TCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTGAGAATAAATATTCTC
AATT
AGATGAAG AG CAACCAATG GAGATTG ATTAAACGAACATG AAAATTATTCTTTTCTTG
GCACTGATAACACTCGCTACTTG
TG AG CTTTATCACTACCAAG AGTGTGTTAGAGGTACAACAGTACTTTTAAAAGAACCTTG CTCTTCTG
GAACATACGAG G G
CAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCTTTAGCACTCAATTTGCTTTTGCTTGTCCT
GACG
G CGTAAAACACGTCTATCAGTTACG TG C CAG ATCAGTTTCACCTAAACTGTTCATCAGACAAG AG
GAAGTTCAAGAACTTT
ACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCTTCACACTCAAAAGAAAGACAGAATGATT
GAA
CTTTCATTAATTGACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTAATTATGCTTATTATCTTTTGGT
TCTCACT
TGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAATTTCTTGTTTTCTTAG
GAATCATCACAACTGTA
GCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTGATGACCCGTGTCCTATTC
ACT
TCTATTCTAAATG GTATATTAGAG TAG G AG CTAGAAAATCAG CACCTTTAATTG AATTGTG CG TGG
ATGAG G CTG GTTCTA
AATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTGCCAGGAACCTAA
ATTG
GGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAGATTTCATCT
AAA
CGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATG
CACCCCGCATTACGTTTGGTGGACCCTCAGATTC
AACTGGCAGTAACCAGAATGGAGAACG
CAGTGGGGCGCGATCAAAACAACGTCGGCCCCAAGGTTTACCCAATAATACT
GCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCTCGAGGACAAG
GCGTTCCAATTAACACC
AATAGCAGTCCAGATGACCAAATTGG
CTACTACCGAAGAGCTACCAGACGAATTCGTGGTGGTGACGGTAAAATGAAAG
ATCTCAGTCCAAGATG
GTATTTCTACTACCTAGGAACTGGGCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGC
ATCATATG G GTTG CAACTG AG G G AG CCTTGAATACACCAAAAGATCACATTG G CAC CCG
CAATCCTG CTAACAATGCTGC
AATCGTG CTACAACTTCCTCAAG GAACAACATTG CCAAAAG G CTTCTACGCAG AAG G GAG CAGAG G
CGG CAGTCAAG CC
TCTTCTCGTTCCTCATCACG TAG TCG CAACAGTTCAAGAAATTCAACTCCAG G CAG CAGTAAACG
AACTTCTCCTGCTAGAA
TG G CTG G CAATG G C GGTGATG CTG CTCTTG CTTTG CTG CTG CTTG ACAGATTGAACCAG
CTTGAGAG CAAAATGTCTG GT
AAAGG
CCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCTAAGAAGCCTCGGCAAAAACGTAC
TGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAACCCAAGGAAATTTTGGGGACCAG
G
AACTAATCAGACAAGGAACTGATTACAAACATTGGCCGCAAATTGCACAATTTGCCCCCAGCGCTTCAGCGTTCTTCG
GAA
TGTCGCGCATTGGCATGGAAGTCACACCTTCGGGAACGTGGTTGACCTACACAGGTGCCATCAAATTGGATGACAAAGA
T
CCAAATTTCAAAG ATCAAGTCATTTTG CTG AATAAG CATATTGACG CATACAAAACATTCCCACCAACAG AG
CCTAAAAAG
GACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCG
CAGAGACAGAAGAAACAGCAAACTGTGACTCTTCTTCCTGC
TGCAGATTTG
GATGATTTCTCCAAACAATTGCAACAATCCATGAGCAGTGCTGACTCAACTCAGGCCTAAACTCATGCAGA
CCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAAT
TCT
CGTAACTACATAG CACAAGTAG ATGTAGTTAACTTTAATCTCACATAG CAATCTTTAATCAG
TGTGTAACATTAG G G AG GA
CTTGAAAGAGCCACCACATTTTCACCGAGGCCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAGGGAGAGCTG

CCTATATG GAAG AG CCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAG
CTTCTTAG GAG NAT
GACANNNNNNNNNNNNNN
SEQ ID NO: 16 >Severe acute respiratory syndrome coronavirus 2 orf1ab polyprotein of isolate hCoV-19/Austria/CeM M0360/2020 M ESLVPG FN E KTHVQLSLPVLQVRDVLVRG FG DSVEEVLSEARQHLKDGTCG LVEVE KGVLPQLEQPYVF
I KRSDARTAPHG H
VMVE LVAELE G I QYG RSG ETLGVLVP HVG El PVAYRKVLLRKNG NKGAGG HSYGADLKSF DLG
DELGTDPYE DFQENWNTKH
SSGVTR EL M RE LNGGAYTRYVDNN FCG P DGYPLECIKDLLARAG KASCTLSEQLDF I DTKRGVYCCRE
HEHEIAWYTERSEKSYE
LQTP F E I KLAKKF DTF NG ECPN FVF PL NSI I KTIQPRVEKKKL DG F MG RI RSVYPVASPN
ECNQMCLSTLM KC DHCG ETSWQTG
DFVKATC EFCGTEN LTKEGATTCGYLPQNAVVKIYCPACH NSEVG PEHSLAEYH NESGLKTILRKGG
RTIAFGGCVFSYVGCHNK

LASFSASTSAFV ETVKG L DYKAF KQIVESC
G N F KVTKG KAKKGAWN IG EQKS I LSPLYAFASEAARVVRS I FSRTLETAQNSVRVLQKAAITI LDG
ISQYSLRLIDAM M FTSDLAT
NN LVVMAYITGGVVQLTSQWLTN I FGTVYE KLKPVLDWL EE KFKEGVEF
LRDGWEIVKFISTCACEIVGGQIVTCAKE I KESVQT
F FKLVNKFLALCADSI I IG GAKLKALN LG ETFVTHS KG LYR KCVKSREETG LLM PLKAPK El IFL
EG ETLPTEVLTEEVVLKTG DLQPL
EQPTSEAVEAPLVGTPVC I NG L M LLE I KDTEKYCALAPN M MVIN NTFTLKGGAPTKVTFG DDTVI
EVQGYKSVN ITFE LDERIDK
VLN E KCSAYTVE LGTEV N E FACVVADAVIKTLQPVS EL LTPLG I D LD EWSMATYY LF DESG
EFKLASH MYCSFYP PDEDE EEG DC
E E EEFE PSTQYEYGTEDDYQGKPLE FGATSAALQPE EEQEEDWLDD DSQQTVGQQDGSE
DNQTTTIQTIVEVQPQLE M E LTP
VVQTIEVNSFSGYLKLTDNVYIKNADIVEEAKKVKPTVVVNAANVYLKHGGGVAGALNKATN NAM QVESD
DYIATNG PLKVG
GSCVLSGH N LAKHCLHVVG PNVNKG ED IQL LKSAYE N F NQH EVLLAPLLSAG I FGAD PI HS
LRVCVDTVRTNVYLAVFDKN LYD
KLVSSFLE M KS EKQVEQKIAE I PK E EVKP FITESKPSVEQRKQDD KKIKACVE EVTTTLEETKFLTEN
LLLYI DING NLH PDSATLVSD
I DITF LKKDAPYIVG DVVQEGVLTAVVI PTKKAGGTTEM LAKALRKVPT DNY ITTYPGQG L NGYTVE
EAKTVLKKC KSAFY ILPSI IS
N EKQEI LGTVSWN LREM LAHAE ETRKLM PVCVETKAIVSTIQR KYKG I KIQE GVVDYGARFYFYTS
KTTVAS LI NTLN DLN ETLVT
M PLGYVTHG LN LE EAARYM RSLKVPATVSVSSPDAVTAYNGYLTSSSKTPE EHFI
ETISLAGSYKDWSYSGQSTQLG I E FLKRG D

KSVYYTSNPTTFHLDGEVITFDNLKTLLSLREVRTIKVFTTVDN IN LHTQVVDMSMTYGQQFG PTYLDGADVTKI
KPH NSH EG KT
FYVLPNDDTLRVEAFEYYHTTDPSFLGRYMSALN HTKKWKYPQVNGLTSIKWADNNCYLATALLTLQQI
ELKFNPPALQDAYYR
ARAGEAAN
FCALILAYCNKTVGELGDVRETMSYLFQHANLDSCKRVLNVVCKTCGQQQTTLKGVEAVMYMGTLSYEQFKKGV
QIPCTCGKQATKYLVQQESPFVM MSAPPAQYELKHGTFTCASEYTGNYQCG
HYKHITSKETLYCIDGALLTKSSEYKGPITDVFY
KENSYTTTI KPVTYKLDGVVCTEI DPKLD NYYKKDNSYFTEQPI DLVP NQPYPNASF DN FKFVCD NI
KFADDLNQLTGYKKPASRE
LKVTFFPDLNGDVVAIDYKHYTPSF KKGAKLLH
KPIVWHVNNATNKATYKPNTWCIRCLWSTKPVETSNSFDVLKSEDAQGM D
NLACEDLKPVSEEVVENPTIQKDVLECNVKTTEVVG DI ILKPAN NSLKITE EVG HTDLMAAYVDNSSLTIKKP
N E LSRVLG LKTLAT
HGLAAVNSVPWDTIANYAKPFLNKVVSTTTNIVTRCLNRVCTNYM PYFFTLLLQLCTFTRSTNSRIKASM
PTTIAKNTVKSVGKF
CLEASF NYLKSP N FSKLI NI I IWF LLLSVCLGSLIYSTAALGVLMSN LGM
PSYCTGYREGYLNSTNVTIATYCTGSIPCSVCLSG LDSL
DTYPSLETIQITISSFKWDLTAFGLVAEWFLAYI LFTRFFYVLGLAAI MQLFFSYFAVH
FISNSWLMWLIINLVQMAPISAMVRMY
IF FASFYYVWKSYVHVVDGCNSSTCM MCYKRNRATRVECTTIVNGVR RSFYVYANGG KG FCKLH
NWNCVNCDTFCAGSTF IS
DEVARDLSLQFKRPINPTDOSSYIVDSVTVKNGSIHLYFDKAGQKTYERHSLSH FVN LDN LRAN NTKGS LP
INVIVF DG KS KCE ES
SAKSASVYYSQLMCQPILLLDQALVSDVGDSAEVAVKM FDAYVNTFSSTFNVPME
KLKTLVATAEAELAKNVSLDNVLSTFISAA
ROG FVDSDVETKDVVECLKLSHQSDI EVTGDSCNNYMLTYN KVE N MTP RDLGACI DCSARH I
NAQVAKSH NIALIWNVKDF M
SLSEQLRKQIRSAAKKN NLPFK LICATTRQVVNVVITKIALKGG KIVN NWLKQLI KVTLVFL FVAAI
FYLITPVHVMSKHTDFSSE I I
GYKAI DGGVTRDIASTDTCFAN K HADFDTW FSQRGGSYTNDKACP LIAAVITREVG FVVPG LPGTI
LRTTNGD F LH FLPRVFSAV
GNICYTPSKLI EYTDFATSACVLAAECTI F KDASG K PVPYCYDTNVL EGSVAYESLRP DTRYVLM DGSI
I QF P NTYLEGSVRVVTTF
DSEYCRHGTCERSEAGVCVSTSG RWVLN NDYYRSLPG VFCGVDAVN [[TN M
FTPLIQPIGALDISASIVAGGIVAIVVTCLAYYF
M RFRRAFG
EYSHVVAFNTLLFLMSFTVLCLTPVYSFLPGVYSVIYLYLTFYLTNDVSFLAHIQWMVMFTPLVPFWITIAYIICISTK

HFYWFFSNYLKRRVVFNGVSFSTFEEAALCTFLLNKEMYLKLRSDVLLPLTQYNRYLALYNKYKYFSGAMDTTSYREAA
CCH [AK
ALN DFSNSGSDVLYQPPQTSITSAVLQSGF R KMAF PSG KVEGC MVQVTCGTTTLNG LW LDDVVYCP
RHVICTSED M LN P NYE
DLLIRKSN HNFLVQAG NVQLRVIG HSMQNCVLKLKVDTANPKTP
KYKFVRIQPGQTFSVLACYNGSPSGVYQCAMRP NFTI KG
SF LNGSCGSVG F NI DYDCVSFCYM H H M ELPTGVHAGTDLEG NI FYG PFVDRQTAQAAGTDTTITVN
VLAW LYAAVI NG DRWF
LNRFTTTLNDFN LVAMKYNYE PLTQDHVDILG PLSAQTGIAVLDMCASLKE LLQNG M NG RTILGSALLE
DE FTP F DVVRQCSGV
TFQSAVK RTI KGTH HWLL LTI LTSLLVLVQSTQWSLF F F LYE NAF LP FAMG I IAMSAFAM M
FVKHKHAFLCLFLLPSLATVAYFN
MVYMPASWVM RI MTW LDMVDTSLSGF KLKDCVMYASAVVLLI LMTARTVYDDGAR RVWT LM
NVLTLVYKVYYG NALDQA
ISMWALIISVTSNYSGVVITVM FLARG IVF MCVEYCPIFFITGNTLQCIMLVYCFLGYFCTCYFG LFCLLN
RYFRLTLGVYDYLVST
QEF RYM NSQG LLPPKNSI DAF KLN I KLLG VG G KPCI
KVATVQSKMSDVKCTSVVLLSVLQQLRVESSSKLWAQCVQLHN DI LLA
KDTTEAFE KM VSLLSVLLSMQGAVDI N KLCEEMLDN RATLQAIASEFSSLPSYAAFATAQEAYEQAVANG
DSEVVLKKLKKSL N
VAKSEFDRDAAMORKLEKMADQAMTQMYKQARSEDKRAKVISAMQTMLFTMLRKLDN DALN NI I N
NARDGCVPLN I IP LT
TAAKLMVVI PDYNTYKNTCDGTTFTYASALWEIQQVVDADSKIVQLSEIS M
DNSPNLAWPLIVTALRANSAVKLQNN ELSPVAL
RQMSCAAGTTQTACTDDNALAYYNTTKGG RFVLALLSDLQDL KWARF PKSDGTGTIYTELE PPCRFVTDTPKG
P KVKYLYFI KG
LNNLNRG MVLGSLAATVRLQAGNATEVP'ANSTVLSFCAFAVDAAKAYKDYLASGGQPITNCVKM
LCTHTGTGQAITVTPEAN
M DQESFGGASCCLYCRCH I DH P NPKG FCDLKG KYVQI PTTCAN DPVG
FTLKNTVCTVCGMWKGYGCSCDQLREPM LQSADA
QSF LNG FAV
SEQ ID NO: 17 >SARS-CoV-2_S_MedUniWien (Sprotein_hCoV19AustriaCeM M03602020) M FVF LVLLP LVSSQCVN LTTRTQLP PAYTNSFTRGVYYPDKVF RSSVLHSTQDLF LP FFSNVTWF HAI
HVSGTNGTK RF DN PVLP
F N DGVYFAST EKSN II RGWIFGTTLDSKTQSLLIVN NATNVVI KVCE FQFCN DP FLGVYYRK N N
KSWM ESEF RVYSSAN NCTF EY
VSQPFLM DLEGKQG NFKN LRE FVF KN I DGYFKIYSKHTP I N LVR DLPQG FSALEP LVDLPIG IN
ITRFQTLLALHRSYLTPGDSSSG
WTAGAAAYYVGYLQPRTFLLKYNE
NGTITDAVDCALDPLSETKCTLKSFTVEKGIYQTSNFRXQPTESIVRFPNITNLCPFG EVFN
ATRFASVYAWN

FTGCVIAWNSNNLDSKVGGNYNYLYRLFRKSNLKPFERDISTEIYQAGSTPCNGVEGFNCYFPLQSYGFQPTNGVGYQP
YRVVV
LSFELLHAPATVCG PKKSTNLVKNKCVN FN F NG LTGTGVLTESN KKF LPFQQFG
RDIADTTDAVRDPQTLE I LDITPCSFGGVSVI
TPGTNTSNQVAVLYQGVNCTEVPVAI
HADQLTPTWRVYSTGSNVFQTRAGCLIGAEHVNNSYECDIPIGAGICASYQTQTNSP
RRARSVASQS1lAYTMSLGAENSVAYSXNSIAIPTNFTISVITEI
LPVSMTKTSVDCTMYICGDSTECSNLLLQYGSFCTQLNRALT
G IAVEQD KNTQEVFAQVKQIYKTP PI KDFGG F NFSQILP DPSKPSKRSFI E DL LF N KVTLADAG
FIKQYG DCLGDIAARDLICAQKF
NG LTVLPPL LTDE M IAQYTSALLAGTITSG WTFGAGAALQI P FAM QMAYRF NG
IGVTQNVLYENQKLIANQFNSAIG KIQDS LS
STASALG KLQDVVNQNAQALNTLVKQLSSN FGAISSVLNDILSRLDKVEAEVQI DRLITG RLQSLQTYVTQQLI
RAAEI RVSAN LA
ATKMSECVLGQSKRVDFCG KGYHLMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDG KA H FP
REGVFVSNGTHWFVTQ
RNFYEPQIITTDNTFVSG NCDVVIG IVNNTVYD PLQPE LDSFKEELDKYFKN HTSPDVDLG DISG I
NASVVNIQK El DRLN EVAKN
LN ESLI DLQELG KYEQYI KWPWYIW LG FIAG LIAIVM VTI M
LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT

SEQ ID NO: 18 > Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/England/ex-5A/2021, EVAg Ref-SKU:004V-04071 (SA_P2) complete genome. South-African B.1.351 lineage ATTAAAGGTTTATACCTTCCCAGGTAACAAACCAACCAACTTTCGATCTCTTGTAG
ATCTGTTCTCTAAACGAACTTTAAAAT
CTGTGTG GCTGTCACTCGG CTG CAT G CTTAGTG CACTCACGCAGTATAATTAATAACTAATTACTGTCGTTG
ACAG GACAC
GAGTAACTCTTCTATCTTCTGCAG G CT G CTTACG G TTTCGTCC G TGTTG CAGCCGATCATCAG
CACATCTAG GTTTTGTCCG
GGTGTG ACCG AAAG G TAAG ATG G AG AG CCTTGTCCCTG G TTTCAACG AG
AAAACACACGTCCAACTCAGTTTGCCTGTTTT
ACAG GTTCGCG ACGTGCTCGTACGTG GCTTTG GAG ACTCCGTGG AG G AG GTCTTATCAG AG GCACG
TCAACATCTTAAAG
ATG GCACTTGTGG CTTAG TAG AAGTTGAAAAAGGCGTTTTG
CCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGG
ATG CTCG AACTG CACCTCATGG TCATGTTATG GTTG AG CTG G TAG CAGAACTCGAAG
GCATTCAGTACGGTCGTAGTG GT
GAG ACACTTGGTGTCCTTGTCCCTCATGTG GGCG AAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAG
AACGGTAAT
AAAG GAG CTG GTG GCCATAGTTACG GCGCCGATCTAAAGTCATTTGACTTAGGCGACGAG CTG
GCACTGATCCTTATGA
AGATTTTCAAGAAAACTG GAACACTAAACATAGCAGTG GTG TTACCCGTG AACTCATG C GTG AG
CTTAACG G AG GG G CAT
ACACTCG CTATGTCG ATAACAACTTCTGTG G CC CTG ATG G CTACC CTCTTG AG TG
CATTAAAGACCTTCTAG CACGTG CTG G
TAAAGCTTCATGCACTTTGTCCG AACAACTG GACTTTATTGACACTAAGAG G GGTGTATACTG CTG
CCGTGAACATG AG CA
TG AAATTGCTTGGTACACG GAACGTTCTGAAAAG AG CTATGAATTG CAGACACCTTTTGAAATTAAATTG G
CAAAG AAATT
TG ACATCTTCAATGGG GAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAG ACTATTCAACCAAGG
GTTG AAAAG
AAAAAGCTTGATG G CTTTATG GGTAGAATTCGATCTG TCTATCCAGTTGCGTCACCAAATG AATG
CAACCAAATGTGCCTTT
CAACTCTCATGAAGTGTG ATCATTGTG GTGAAACTTCATG G CAG AC GGG CGATTTTGTTAAAGCCACTTG
CGAATTTTGTG
GCACTG AG AATTTGACTAAAG AAG G TG CCACTACTTGTGGTTACTTACCCCAAAATG
CTGTTGTTAAAATTTATTGTCCAG C
ATGTCACAATTCAGAAGTAG G ACCTG AG CATAGTCTTG CCG AATACCATAATGAATCTG
GCTTGAAAACCATTCTTCGTAA
GG GTG GTC GCACTATTG CCTTTG G AG GCTGTGTGTTCTCTTATGTTGGTTG CCATAACAAGTG
TGCCTATTG GGTTCCACGT
GCTAGCGCTAACATAG GTTGTAACCATACAGGTGTTGTTG GAG
AAGGTTCCGAAGGTCTTAATGACAACCTTCTTG AAATA
CTC CAAAAAG AG AAAGTCAACATCAATATTGTTG GTGACTTTAAACTTAATGAAGAGATCG
CCATTATTTTGGCATCTTTTT
CTGCTTCCACAAGTGCTTTTG TGG AAACTGTGAAAGGTTTGGATTATAAAG CATTCAAACAAATTG
TTGAATCCTGTG G TA
ATTTTAAAGTTACAAAAG G AAAAG CTAAAAAAGGTGCCTGGAATATTG GTG AACAGAAATCAATACTG
AGTCCTCTTTATG
CATTTG CATCAG AG G CTG CTCG
TGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTG CGTGTTTTA
CAG AAGG CCGCTATAACAATACTAG ATGG AATTTCACAGTATTCACTG AG ACTCATTG ATG CTATG
ATGTTCACATCTG ATT
TG GCTACTAACAATCTAGTTGTAATGGCCTACATTACAG GTG GTGTTGTTCAGTTG
ACTTCGCAGTGGCTAACTAACATCTT
TG GCACTGTTTATG AAAAACTCAAACCCGTCCTTGATTG GCTTG AAGAG AAGTTTAAG GAAG GTG TAG
AGTTTCTTAG AG A
CGGTTG GG AAATTG TTAAATTTATCTCAACCTG TGCTTGTG AAATTGTCGG TGG
ACAAATTGTCACCTGTGCAAAG GAAAT
TAAG GAG AGTGTTCAGACATTCTTTAAG CTTGTAAATAAATTTTTGGCTTTGTGTGCTG
ACTCTATCATTATTGGTGG AG CT
AAACTTAAAGCCTTGAATTTAG GTGAAACATTTGTCACGCACTCAAAGGG ATTGTACAG
AAAGTGTGTTAAATCCAG AG AA
GAAACTG G CCTACTCATGCCTCTAAAAG CCCCAAAAG AAATTATCTTCTTAG AG GG AG
AAACACTTCCCACAGAAG TGTTA
ACAG AG GAAGTTGTCTTGAAAACTG G TGATTTACAACCATTAGAACAACCTACTAGTG AAG CTGTTG AAG
CTC CATTG G TT
GGTACACCAGTTTGTATTAACG GGCTTATGTTGCTCGAAATCAAAGACACAG AAAAGTACTGTG
CCCTTGCACCTAATATG
ATG GTAACTAACAATACCTTCACACTCAAAG GCG GTG CACCAACAAAGGTTACTTTTG
GTGATGACACTGTGATAGAAGTG
CAAG GTTACAAG AG TGT G AATATCACTTTTG AACTTGATG AAAGGATTG ATAAAGTACTTAATG AG
AAG TG CTCTG CCTAT
ACAGTTG AACTCG GTACAG AAGTAAATG AG TTCG CCTGTGTTGTGGCAG
ATGCTGTCATAAAAACTTTGCAACCAGTATCT
GAATTACTTACACCACTG G G CATTG ATTTAG ATG AG TG G AGTATGG CTACATACTACTTATTTG ATG
AG TCTG GTG AG TTTA
AATTGG CTTCACATATGTATTGTTCTTTTTACCCTCCAG ATG AG GATG AAGAAGAAG GTG ATTGTG AAG
AAGAAGAGTTTG
AG C CATCAACTCAATATG AGTATGGTACTGAAGATG ATTACCAAGGTAAACCTTTGGAATTTG
GTGCCACTTCTG CTG CTCT
TCAACCTG AAGAAG AG CAAGAAG AAGATTG GTTAGATGATG ATAGTCAACAAACTGTTGG TCAACAAGACG
G CAG TG AG
GACAATCAG ACAACTACTATTCAAACAATTGTTG AG GTTCAACCTCAATTAG AG ATG
GAACTTACACCAGTTGTTCAG ACTA
TTGAAGTGAATAGTTTTAG TGG TTATTTAAAACTTACTGACAATGTATACATTAAAAATG CAGACATTGTGG
AAG AAGCTA
AAAAG GTAAAACCAACAGTG GTTGTTAATGCAGCCAATGTTTACCTTAAACATGG AG GAG GTGTTG CAGG
AG CCTTAAAT
AAG GCTACTAACAATGCCATGCAAGTTGAATCTG ATGATTACATAG CTACTAATG G AC CACTTAAAGTG G
GTG G TAGTT GT
GTTTTAAGCG GACACAATCTTG
CTAAACACTGTCTTCATGTTGTCGGCCCAAATGTTAACAAAGGTGAAGACATTCAACTTC
TTAAG AG TG CTTATG AAAATTTTAATCAG CACGAAGTTCTACTTG CACCATTATTATCAG CTG
GTATTTTTG GTG CTG AC CCT
ATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAG
CTGTCTTTGATAAAAATCTCTATGACAAACT
TGTTTCAAG CTITTTG GA AATGAAGAGTGAAAAG CAAGTTG AACAAAAGATCG CTG AGATTCCTAAAG AG
GAAGTTAAG C
CATTTATAACTG AAAGTAAACCTTCAGTTG AACAG AG AAAACAAGATGATAAG AAAATCAAAG
CTTGTGTTGAAGAAGTT
ACAACAACTCTGG
AAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTGACATTAATGGCAATCTTCATCCAGATT
CTG CCACTCTTGTTAGTG ACATTG ACATCACTTTCTTAAAG AAAGATG CT CCATATATAG TG G GTG
ATGTTGTTCAAG AG GG
TGTTTTAACTG CTGTGGTTATACCTACTAAAAAGGCTG GTG GCACTACTG AAATGTTAGCGAAAG CTTT G
AG AAAAGTG CC

AACAGACAATTATATAACCACTTACCCG G GTC AG G GTTTAAATG GTTA CACTG TAG AG GAG G
CAAAGACAGTG CTTAAAA
AG T G TAAAAG T G CCTTTTA CATTCTAC CATCTATTAT CTCTAATG A G AAG CAA G AAATT
CTTG G AACTGTTTCTTG GAATTTG
CG AG AAAT G CTTG CAC ATG C AG AAG AAACACG CAAATTAATG CCT G T CT G TG TG
GAAACTAAAG CCATAGTTTCAACTATA
CAG CGTAAATATAAG G GTATTAAAATACAAG AG G GTGTG GTTGATTATG GTG CTAG ATTTTACTTTTA
CACCAG TAAAA CA
ACT G TAG CGTCACTTATCAACACACTTAAC GATCTAAATGAAACTCTTGTTACAATG CCACTTG G
CTATGTAACACATGG CT
TAAATTTG GAAG AAG CTG CT C G G TATAT G AG ATCTCT CAAAG TG CC AG CTAC AGTTTCT G
TTTCTT CACCT G ATG CTGTTAC
AG C G TATAATG GTTATCTTACTTCTTCTTCTAAAACACCTGAAG AACATTTTATTG AAACC ATCT CACTT
G CT G G TTCCTATA
AAG ATTG GTCCTATTCTG G ACAATCTACACAACTAG GTATAG AATTTCTTAAG AG AG
GTGATAAAAGTGTATATTACACTA
GTAATCCTACCACATTCCACCTAG ATG GTG AAGTTATCACCTTTGACAATCTTAAG ACACTT CTTT
CTTTGAG AGAAGTG AG
GACTATTAAG G TG TTTACAA CA GTA G ACAA CATTAAC CTC CACAC G CAAGTTGTG
GACATGTCAATG ACATATG G A CAA CA
GTTTG GTCCAACTTATTTG GATG G AG CTG ATG TTACTAAAATAAAACCTCATAATTCAC ATG AA G G
TAAAACATTTTAT G TT
TTACCTAATG AT G ACA CTCTA CG T G TTG AG G CTTTT G AG TACTA CCACAC AACTG ATCC
TAG TTTTC TG G G TAG GTACATGT
CAG CATTAAATCACACTAAAAATTG G AAATA CC CACAAG TTAATG G TTTAACTTCTATTAAATG G G
CAG ATAACAACTGTTA
TCTTG CCACTG CATTG TTAAC ACTC CAACAAATAG A G TTG AA G TTTAATCCAC CT G
CTCTACAAG ATG CTTATTACAG AG CA
AG G G CT G GTG AAG CTG CTAACTTTTGTG CA CTTATCTTA G CCTACTGTAATAAG ACAG TAG G
TG AG TTAG GTG ATG TTAG A
G AAACAATG AG TTACTTG TTTCAA CATG CCAATTTAG ATTCTTG CAAAAG AGTCTTGAACGTG
GTGTGTAAAACTTGTG GA
CAAC AG CAG ACAAC CCTTAAG G G TG TAG AAG CTGTTATGTACATG G G CACACTTTCTTATG
AACAATTTAAGAAAG GTG TT
CAG ATACCTTGTACGTGTG GTAAACAAG CTACAAAATATCTAGTACAACAG GAGTCACCTTTTGTTATG ATG
TCAG CACCA
CCTG CT CAG TATG AA CTTAA G CAT G GTACATTTACTTGTG CTAG TG AG TACACTG
GTAATTACCAGTGTG GT CACTATAAAC
ATATAACTTCTAAAGAAACTTTGTATTG CATAG ACG GTG CTTTACTTACAAAGTCCTCAGAATACAAAG
GTCCTATTACG GA
TGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTG GATG G TG TTG TTT G
TA CAG AAATT
G AC CCTAAG TTG G ACAATTATTATAAG A AAG ACAATT CTTATTT CACAG AG CAAC CAATT G
ATCTTG TA CC AAACC AACC AT
ATCCAAACG CAAG CTTCGATAATTTTAAGTTTGTATGTG ATAATATCAAATTTG
CTGATGATTTAAACCAGTTAACTG GTTA
CAAG AAACCTG CTTCAAG AG AG CTTAAAGTTACATTTTTCCCTG A CTTAAATG GTG ATGTG GT G G
CTATTGATTATAAACAC
TAC ACAC C CTCTTTTAAG AAA G GAG CTAAATTGTTACATAAACCTATTGTTTG G CATGTTAACAATG
CAACTAATAAAG C CA
C G TATAAACCAAATAC CT G GTG TATAC G TT G TCTTTG GAG C ACAAAAC CAG TTG AAA
CATCAAATTC G TTT G ATG TACTG AA
G T CAG AG G AC G CG C AG G G AATG GATAATCTTG C CT G CG AAG AT CTAAAACC AG
TCTCTG AAG AAG TAG TG GAAAATCCTA
CCATACAG AAAGACGTTCTTG AG TG TAATGTG AAAACTACCG AAG TT GTAG G AG
ACATTATACTTAAACC AG CAAATAATA
G TTTAAA AATTA CAG AAG AG GTTG G C CAC ACA G AT CTAATG G CTG
CTTATGTAGACAATTCTAGTCTTACTATTAAGAAAC
CTAATG AATTATCTAG AG TATTAG GTTTGAAAACCCTTG CTACTCATG GTTTAG CT G CT
GTTAATAGTGTCCCTTG G G ATAC
TATA G CTAATTATG CTAAG CCTTTTCTTAACAAAGTTG TTAG TACAACTACTAACATA G TTA CA C G
G TG TTTAAA CC GT G TTT
GTACTAATTATATG CCTTATTTCTTTACTTTATTG CTAC AATTG TG TA CTTTTACTAG AAG
TACAAATTCTAG AATTAAA G CAT
CTATG CC G ACTACTATAG CAAA G AATA CTG TTAAG AG TG TC G G TAAATTTT G TCTAG AG
GCTTCATTTAATTATTTGAAGTC
ACCTAATTTTTCTAAACTGATAAATATTATAATTTG GTTTTTACTATTAAGTGTTTG CCTAG GTTCTTTAAT
MTACTCAACCG
CTG CTTTAG G TGTTTTAATGTCTAATTTAGG CATG CCTTCTTACTGTACTG GTTACAG AG AAG
GCTATTTG AACTCTACTAAT
GTCACTATTG CAA CCTACTG TACT G G TTCTATACCTTG TAG TG TTT G TCTTAG T G GTTTAG
ATT CTTTAG ACA CCTAT CCTT CT
TTAG AAA CTATACAAATTACCATTT CATCTTTTAAATG GGATTTAACTG CTTTTG G CTTAGTTG CAG
AGTG GTTTTTG G CATA
TATTCTTTTCACTAG GTTTTTCTATGTACTTG GATTG G CTGCAATCATG CAATTGTTTTTCAG CTATTTTG
C AG TAC ATTTTAT
TAG TAATTCTTG G CTTATGTG GTTAATAATTAATCTTG TA CAAATG G CCC CGATTTCAG CTATG GTT
AG AATGTAC ATCTTCT
TTG CATCATTTTATTATGTATG G AAAAGTTATGTG CATG TTG TAG ACG GTTGTAATTCATCAACTTGTAT
G ATG TG TTA CAA
AC G TAATAG AG C AA CAA G AG TC G AATG TACAACTATTG TTAATG GTGTTAGAAG GT
CCTTTTAT G TCTATG CTAATG GAG G
TAAAGG CTTTTG CAAACTACACAATTG GAATTGTGTTAATTG TGATACATTCTGTG CTG G TAG
TACATTTATTAG T G ATG AA
GTTG CG AG AG ACTT G TCACTACAG TTTAAAAG A CCAATAAATC CTACTG
ACCAGTCTTCTTACATCGTTGATAG TGTTACAG
TG AAGAATG GTTCCATCCATCTTTACTTTGATAAAG CTG GTCAAAAGACTTATG AAA G A CATT CTCT
CTCTC ATTTTG TTAAC
TTAG ACAACCTG AG AG CTAATAACACTAAAG G TT CATTG CCTATTAATGTTATAGTTTTTGATGG
TAAATCAAAATG TGAAG
AATCATCTG CAAAATCAG C GT CTG TTTACTACA G TCAG
CTTATGTGTCAACCTATACTGTTACTAGATCAG G CATT AG TG TC
TG ATG TT G GTGATAGTG CG G AAG TT G CAG TTAAAATG TTTG AT G
CTTACGTTAATACGTTTTCATCAACTTTTAACGTACCA
ATG GAAAAACTCAAAACACTAGTTG CAACTG CAG A AG CT G AACTTG CAAAGAATGTGTC CTTAG A
CAAT GTCTTATCTACT
TTTATTTCAG CAG CT C G G CAAG G GTTTGTTGATTCAG ATG TAG AAA CTAAA G ATG TTG TTG
AATG T CTTAAATTG TCAC ATC
AATCTGACATAG AAGTTACTG G CG ATAGTTGTAATAACTATATG CT CACCT ATAAC AAAG TTG
AAAACATG ACACC CC GTG
ACCTTG G TG CTTGTATTG ACTG TAG TG CG CGTCATATTAATG CG CA G GTAG CAAAAAGTCA CAA
CATTG CTTTGATATG GA
AC G TTAAAG ATTT CAT G TC ATTG TCTG AAC AA CTAC G AAAAC AAATAC G TAG TG CTG
CTAAAAAG AATAACTTACCTTTTAA
G TTG AC ATG T G CAACTACTAG ACAAG TT GTTAATGTTGTAACAACAAAG ATAG CA CTTAA G G
GTG GTAAAATTGTTAATAA
TTG GTTG AAG CAG TTAATTAAAGTTACACTTG TG TT CCTTTTTG TTG CTG
CTATTTTCTATTTAATAAC AC CTG TT CATG TC AT
GTCTAAACATACTGACTTTTCAAGTGAAATCATAG GATACAAG G CTATTGATG GTG
GTGTCACTCGTGACATAG CAT CTAC

AG ATACTTG TTTTG CTAACAAACATG CTG ATTTTG A CACAT G GTTTAG CCAGCGTG GTGG TAG
TTATACTAAT G ACAAAG CT
TG CCCATTGATTG CTG CAGTCATAAC AAG AG AAGTG G GTTTTG TCGTG CCTG GTTTG CCTG G
CACGATATTACG CACAACT
AATG GT G ACTTTTT G CATTTCTTACCTAG A G TTTTTAG TG C AG TTG G TAACAT CTG TTACA
C AC CAT CAAAACTTATAG AG TA
CACTGACTTTG CAACATCAG CTTGTGTTTTG G CTG CTG AATGTACAATTTTTAAAGATG CTTCTG
GTAAGCCAGTACCATAT
TGTTATGATACCAATGTACTAGAAG GTTCTGTTG CTTATGAAAGTTTACG CCCTGACACACGTTATGTG CT
CATG GATG G CT
CTATTATTCAATTTCCTAACACCTACCTTG AAG GTTCTGTTAG AG TG GTAACAACTTTTGATTCTG AG TA
CTG TAG G CACG G
CACTTGTGAAAG ATCAGAAG CTG G TG TTTG T G TAT CTACTAG TG G TAG ATGG G TA CTTAA C
AAT G ATTATTACAGATCTTTA
CCAG GAG TTTTCTG TG GTG TAG ATG CTG
TAAATTTATTTACTAATATGTTTACACCACTAATTCAACCTATTG GTG CTTTG GA
CATATCAG CAT CTATAG TAG CTG GTGGTATTGTAG CTATCGTAGTAACATG CCTTG C
CTACTATTTTATG AG GTTTAG AAG A
G CTTTTGGTG AAT ACAGTCATG TAG TTG CCTTTAATACTTTACTATTCCTTATGTCATT CACTG TACT
CTG TTTAA CACCA GTT
TACTCATTCTTACCTG G TG TTTATTCT G TTATTTACTT G TACTTG A CATTTTATCTTACTAATG
ATGTTTCTTTTTTAG CACATA
TT CAG T G G AT G G TTAT GTTC ACACCTTTAG TACCTTTCTG G ATAACAATTG
CTTATATCATTTGTATTTCCACAAAG CATTTCT
AUG GTT CTTTAG TAATTACCTAAAG AG ACGTGTAG TCTTTAATG GTGTTTCCTTTAGTACTTTTG
AAGAAG CTG CG CT G TG
CAC CTTTTTG TTAAATAAAG AAATGTATCTAAAGTTG CG TA G TG ATGTG CTATTACCTCTTACG
CAATATAATAG ATACTTA
G CTCTTTATAATAAGTACAAGTATTTTAGTGG AG CAATG GATACAACTAG CTA CAG AG AAG CTG CTTG
TT G TCATCTCG CA
AAG G CTCTCAATGACTTCAGTAACTCAG G TTCT G AT G TTCTTTA CCAAC C ACCAC AAAC CTCTAT
CACCTCAG CTGTTTTG CA
G AG TG GTTTTAGAAAAATG G CATTCCCATCTG GTAAAG TT G AG G GTTGTATG GTACAAG
TAACTTGTG GTACAACTACACT
TAACGGTCTTTG G CTTG ATG AC GTAG TTTA CTGTCCAAG ACATGTG ATCTG CAC CTCTG AAG
ACATG CTTAACCCTAATTAT
G AA G ATTTACT CATT CG TAAG TCTAATCATAATTTCTTG G TACA G G CT G G TAATG TTCA
ACTCA G G GTTATTGG ACATTCTA
TG CAAAATTGTGTACTTAAG CTTAG GGTTG ATACAG CCAATCCTAAGACACCTAAGTATAAGTTTGTTCG
CATTCAACCAG
G AC AG ACTTTTTCAG TG TTAG CTTGTTACAATG G TTCACCAT CT G GTGTTTACCAATGTG CTATG
AG G CCCAATTTCACTATT
AAG G GTTCATTCCTTAATG G TT CATG T G G TAG TG TTG GTTTTAACATAG ATTAT G ACT G TG
TCTCTTTTT KTTAC ATG C AC CA
TAT G GAATTACCAACTG G AG TTCAT G CTG G C AC AG ACTTA G AAG GTAACTTTTATG G AC
CTTTTGTTG A CA G G CAAACAG C
ACAAGCAG CTG G TA CG GACACAACTATTACAGTTAATGTTTTAG CTTG G TTG TA CG CT G
CTGTTATAAATG G AG ACAG GTG
GTTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTG G CTATGAAG TAC AATTAT G
AACYTCTAACACAA G ACC
ATGTTG ACATACTAG G ACCTCTTTCTG CTCAAACTG GAATTG CCG TTTTAG AT ATG TGTG
CTTCATTAAAAGAATTACTG CA
AAATGGTATGAATG G AC GTACCATATTG G GTAGTG
CTTTATTAGAAGATGAATTTACACCTTTTGATGTTGTTAGACAATG
CTCAG GTGTTACTTTCCAAAGTG CAGTGAAAAG AACAATCAAG G GTACACACCACTG
GTTGTTACTCACAATTTTGACTTCA
CTTTTAGTTTTAGTCCAG AG TACTCAATG GTCTTTGTTCTTTTTTTTGTATGAAAATG CCTTTTTACCTTTTG
CT ATG G GTATT
AUG CTATGTCTGCTTTTG CAATGATGTTTGTCAAACATAAG CAT G CATTTCT CTG TTTG TTTTTG TT
ACCTT CTCTTG CCACT
G TAG CTTATTTTAATATG GTCTATATG CCTG CTAGTTG G GTG ATG CGTATTATG ACATG GTTG
GATATG G TTG ATACTAG TT
TG NNNNNNAAG CTAAAAGACTGTGTTATGTATG CAT CAG CTG TAG TG TTACTAATCCTTATG ACAG
CAAGAACTGTGTAT
GATGATG GTG CTAG GAG AGTGTG G ACACTTATGAATGTCTTG ACACTCGTTTATAAAGTTTATTATG
GTAATG CTTTAG AT
CAAG CCATTTCCATGTG G G CTCTTATAATCTCTGTTACTTCTAACTACTCAG GTG TAG TTACAACTG TC
ATG TTTTT G G CC AG
AG G TATTGTTTTTATG T G TG TTG AG TATTG
CCCTATTTTCTTCATAACTGGTAATACACTTCAGTGTATAATG CTAGTTTATT
GTTTCTTAG G CTATTTTTGTACTTGTTACTTTG G CCTCTTTTGTTTACTCAACCG CTACTTTAG ACT G
ACT CTTG GTGTTTATG
ATTACTTAGTTTCTACACAG G AG TTTAG ATATATG AATTCACAG G GACTAYTCCCACCCAAGAATAG
CATAGATG CCTTCAA
ACT C AAC ATTAAATTGTTG G GTGTTG GTGG C AAACCTTG TATCAAAG TA G CCACTG TACAG T
CTAAAATG T C AG AT G TAAA
GTG CAC ATCAG TAG T CTTA CTCT C AG TTTTG CAACAACTCA G AG TAG AAT CATC
ATCTAAATTG TG G G CT C AAT G TG T CCAG
TTACACAATG AC ATTCTCTTAG CTAAAGATACTACTGAAG CCTTTG AAAAAATG G TTTC A CTACTTT
CT G TTTTG CTTTCCAT
G C AG G GTG CT G TAG ACATAAACAAG CTTTGTG AAGAAATGCTG G A CAA CAG G G
CAACCTTACAAG CTATAG C CTCAG AG T
TTAG TT CCCTT CCAT CATAT G CAG CTTTTG CTACTG CTCAA G AAG CTTAT G AG CAG G CTG
TT G CTAATG GTGATTCTG AAGT
TGTTCTTAAAAAGTTGAAG AAGTCTTTGAATGTG GCTAAATCTG AATTTG ACC G TG ATG CAG CCATG
CAACGTAAGTTG GA
AAAG ATG G CTG ATCAAG CTATG A CCCAAATG TATAAACA G G CTA G AT CTG AG G A CAAG
AG G G CAAAAGTTACTAGTG CTA
TG CAG AC AATG CTTTTCACTATG CTTAG AAAG TT G GATAATGATG
CACTCAACAACATTATCAACAATG CAAG AG ATG G TT
GTGTTCCCTTGAACATAATACCTCTTACAACAG CAG CCAAACTAATG GTTGTCATACCAG
ACTATAACACATATAAAAATAC
GTGTGATGGTACAACATTTACTTATG CATCAG CATTGTG G G AA ATCCAACAG G TTG TAG AT G CAG
ATAGTAAAATTGTTCA
ACTTAGTGAAATTAGTATG G ACAATTC A CCTAATTTAG CATG G CCTCTTATTGTAACAG CTTTAAG G G
CCAATTCTG CTGTC
AAATTAC AG AATAATG AG CTTA G TC CTG TT G CACTACGACAGATGTCTTGTG CT G CCG
GTACTACACAAACTG CTTG C ACT
G AT G ACAATG CGTTAG CTTACTACA ACA CAA CAAAG G G AG G TAG GTTTGTACTTG
CACTGTTATCCG ATTTACAGGATTTG
AAATGG G CTAG ATTCCCTAAGAGTGATG G AACTG GTACTATCTATACAG AACTG G AA CCACCTTGTAG
GITTG TTACAG AC
ACACCTAAAG GTCCTAAAGTG AAGTATTTATACTTTATTAAAG G ATTAAACAAC CTAAATAG AG GTATG
GTACTTG GTA GT
TTAG CTG CCA C AG TAC GTCTACAAG CTG GTAATG CAA CAG AAG TG C CTG
CCAATTCAACTGTATTATCTTTCTGTG CTTTTG
CTG TAG ATG CTG CTAAAG CTTACAAAGATTATCTAG CTAGTG G G GG AC AACCAATCACTAATTG TG
TTAAG ATG TTG TG TA

CAC ACACTG GTACTG GTCAG G CAATAACAGTTACACCG GAAG CC AATATG G AT CAAG AATCCTTTG
GTG GTG CATCG TG TT
G T CT G TACTG CC G TTG CCACATAGATCATCCAAATCCTAAAG G ATTTTGTG ACTTAAAAG
GTAAGTATGTACAAATACCTAC
AACTTGTG CTAATG AC CCTGTG G GTTTTACACTTAAAAACACAGTCTGTACCGTCTG CG GTATGTG
GAAAG GTTATG GCTG
TAG TTG TG AT CAACTCCG CG AACCCATG CTTCAGTCAG CTG ATG CA CAATC GTTTTTAAACG G
GTTTG CG GTGTAAGTG CA
G CCCGTCTTACACCGTG CG G CACAG G CACTAG TACTG ATGTCG TATAC AG GG CTTTTG ACAT
CTACAATG ATAAAG TAG CT
G GTTTTG CTAAATTCCTAAAAACTAATTGTTGTCG CTTCCAAGAAAAG G AC G AAGATGACAATTTAATTG
ATTCTTACTTTG
TAG TTAAG AG ACACACTTTCTCTAACTACCAACATG AA G AAAC AATTTATAATTTACTTAAG
GATTGTCCAG CTGTTG CTAA
ACATGACTTCTTTAAGTTTAG AATAGACG GTGACATG GTACCACATATATCACG TCAACG
TCTTACTAAATACACAATG G CA
G AC CTC G TCTATG CTTTAAG G CATTTTGATGAAG GTAATTGTGACACATTAAAAG
AAATACTTGTCACATACAATTGTTGTG
ATG ATG ATTATTTCAATAAAAAG G A CTG GTATG ATTTTG TAG AAAA CCCAG ATATATTAC G
CGTATACG CCAACTTAG GTG
AACGTGTACG CC AAG CTTT GTTAAAAA C AG TA CAATT CTG T G ATG CCATG CGAAATG CT G
GTATTGTTG GTGTACTG ACAT
TAG ATAATCAAGATCTCAATG G TAACTG GTATGATTTCG GTGATTTCATACAAACCACG CCAG G TAG TG
G A G TTCCTG TTG
TAG ATTCTTATTATTCATTGTTAATG CCTATATTAAC CTT G ACC AG G GCTTTAACTG CAG AG T
CACAT G TT G ACACTG ACTTA
ACAAAG CCTTACATTAAGTGG G ATTTGTTAAAATATG ACTTCACG G AAG AG AG
GTTAAAACTCTTTGACCGTTATTTTAAAT
AUG GG ATCAG ACATACCACCCAAATTGTGTTAACTGTTTG GATG ACAG ATG CATTCTGCATTGTG
CAAACTTTAATGTTTT
ATTCTCTACAGTGTTCCCACTTACAAGTTTTG G AC C ACTA G TG A G AAAAATATTTG TTG AT G G
TG TTC CATTTG TAG TTTCAA
CTG GATACCACTTCAG AG AG CTAG GTGTTGTACATAATCAG GATGTAAACTTACATAG CT CTAG
ACTTAGTTTTAAGG AAT
TACTTG TG TAT G CT G CTG ACCCTG CTATG CA C G CTG CTTCTG GTAATCTATTACTAGATAAACG
CACTACGTG CTTTTCAGT
AG CTGCACTT ACTAA CAATG TTG CTTTTCAAACTGTCAAACCCG GTAATTTTAACAAAG
ACTTCTATGACTTTG CTGTGTCTA
AG G GTTTCTTTAAG GAAG G AAGTTCTGTTG AATTAAAACACTTCTTCTTTG CT CAG G ATG GTAATG
CTG CTATCAG CGATTA
TG ACTACTATCGTTATAATCTACCAACAATGTGTG ATAT CAG AC AACTACTATTTG TAG TT G AAG TTG
TTG ATAAG TA CTTT
GATTGTTACG ATG GTG G CTGTATTAATG CTAACC AAG T CATC G TCAA CAACCTAG AC AAATC AG
CT G GTTTTCCATTTAATA
AATG GG GTAAG G CTAGACTTTATTATG ATTC AATG AGTTATG AG GATCAAGATG
CACTTTTCGCATATACAAAACGTAATG
T CATC CCTACTATAA CTCAAATG AAT CTTAA G TAT G CC ATTAG T G CAAA G AATA G AG CT
C G CA CC G TAG CTG GTGTCTCTAT
CTG TAG TACTATG ACCAATAG ACAG TTTC ATCAAAAATTATTG AA ATCAATAG CC G C CA CTAG
AGG AG CTACTGTAGTAAT
TG GAACAAG CAAATTCTATGGTG GTTG G CACA ACATG TTAAAAACTG TTTATAG T G AT G TA G
AAAACC CT CAC CTTATG G G
TTG G G ATTATCCTAAATGTG ATAG AG CCATG CCTAACATG CTTAGAATTATG G CCTCACTTGTTCTTG
CTCG CAAACATACA
ACG TGTTG TAGCTTGTC ACACCG TTT CTATAG ATTAG CTAATG AG TG TG CT CAAG TATTG AGTG
AAATG GTCATGTGTG G C
G GTTCACTATATGTTAAACCAG GTG GAACCTCATCAG GAG ATG CCACAACTG CTTATG
CTAATAGTGTTTTTAACATTTGTC
AAG CTGTCACG G CCAATGTTAATG CACTTTTATCTACTGATG GTAACAAAATTG CCG ATAAGTATGTCCG
CAATTTACAAC
ACAG ACTTTATG AG TG TCTCTATA G AAATAG AG ATG TTG A CA CAG ACTTTG TG AATG A G
TTTTAC G CATATTTGCGTAAAC
ATTTCTCAATG ATGATACTCTCTG AC G AT G CTGTTGTGTGTTTCAATAG CACTTATG CATCTCAAG
GTCTAGTG G CTAG CAT
AAAG AACTTTAAGTCAGTTCTTTATTATCAAAACAATGTTTTTATGTCTGAAG CAAAATGTTG G ACTG AG
ACTG ACCTTACT
AAAG G ACCTCATGAATTTTG CTCTCAACATACAATG CTAG TTAAA CA G G G TG AT G ATTATG T G
TAC CTTC CTTA CCCAG ATC
CATCAAGAATCCTAG G G G CCG G CTG TTTTG TAG ATGATATCGTAAAAACAGATG GTACACTTATG
ATTGAACG GTTCGTGT
CTTTAG CTATAGATG CTTACCCACTTACTAAACATCCTAATCAG GAG TAT G CT G AT G TCTTTCATTTG
TACTTACAATACATA
AG AAA G CTACATG ATG AGTTAACAG G ACAC ATG TTAG AC ATG TATTCTG TTATG C
TTACTAATG ATAAC ACTT CAAG G TATT
G G G AACCTG AG TTTTATG AG GCTATGTACACACCG CATACAGTCTTACAG GCTGTTGG G G
CTTGTGTTCTTTG CAATT CAC
AG A CTTC ATTAA G ATG TG GTG CTTG CATAC G TAG ACC ATTCTTAT G TTG TAAAT G
CTGTTACG ACCATGTCATATCAACATC
ACATAAATTAGTCTTGTCTGTTAATCCGTATGTTTGCAATG CTTCAG GTTGTGATGTCACAG ATG T G A CT
CAACTTTACTTAG
GAG GTATG AG CTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTG CTAATG
GACAAGTTTTTG GTTTATAT
AAAAATACATGTGTTG GTAG CGATAATGTTACTG ACTTTAATG CAATTG CAACATGTGACTG GACAAATG
CTG GTG ATTAC
ATTTTAG CTAAC ACCTG TACT G AAAG ACTCAAG CTTTTTG CAG CAG AA AC G CT CAAAG CTACT
G AG G AG A C ATTTAAACT G
TCTTATG G TATTG CT ACTG TAC G T G AAG TG CT G TCT G ACAG AG AATTACAT CTTTC ATG
G GAAGTTG G TAAA C CTAG A CCA
CCA CTTAA CC G AAATTAT G TCTTTACT G GTTATCG TGTAACTAAAAACAG TAAAGTACAAATAG G A
G AG TACACC TTT G AA
AAAG GTG ACTATG GTGATG CTG TTG TTTAC C G AG GTACAACAACTTACAAATTAAATGTTG GTG
ATTATTTTGTG CTGACAT
CACATAC AG TAAT G CC ATTAAG TG CACCTACACTAGTG CCACAAG AG CA CTATG TTAG
AATTACTG G CTTATACCCAACACT
CAATATCT CAG AT G AG TTTTCTAG CAATGTTG CAAATTATCAAAAG GTTG G TATG
CAAAAGTATTCTACACTCCAG G GACCA
CCTG GTACTG GTAAG AG T CATTTTG CTATTG G CCTAG CTCTCTACTACCCTTCTG CTCG CATAG TG
TATA CAG CTTG CTCT CA
TG CC G CTG TT G AT G CACTATG TG AG AAG G CATTAAAATATTTG CCTATAG ATAAAT G TAG
TAG A ATTATACCT G C AC G TG C
TC G T G TA G A G TG TTTTG ATAAATTCAA A G TG AATT CAACATTA G A A CA G TATGT
CTITTG TA CTG TAAATG CATTG CCTG A G
ACG ACAG CAGATATAGTTGTCTTTG ATG AAATTTCAATG G CCACAAATTATG ATTTG AGTGTTGTCAATG
CCAG ATTAC GT
G CTAAG CACTATGTGTACATTG GCG ACCCTG CT CAATTACCTG CACCACGCACATTG CTAACTAAG G G
CACACTAGAACCA
G AATATTTCAATTCAG TG TG TAG ACTTATG AAAACTATAG GTCCAGACATGTTCCTCG G AACTTGTCG
G CGTTGTCCTG CTG
AAATTG TTG AC ACTG T G AG TG CTTTG GTTTATGATAATAAG CTTAAAG CAC ATAAAG
ACAAATCAG CTCAATG CTTTAAAAT

GTTTTATAAG G GTGTTATCACG CATG ATG TTTC AT CTG CAATTAACAG G CCACAAATAG G CGTG
GTAAG AG AATTCCTTAC
AC G TAACCCT G CTTG G AG AAAAG CTG TCTTTATTTC ACCTTATAATTCAC AG AAT G CTG TAG
CCTCAAAGATTTTG G G ACTA
CCAACTCAAACTG TTG ATTCATC A CAG G G CTC AG AATATG ACTATG T C ATATTCACT CAAAC
CA CTG AAAC AG CTCA CT CTT
GTAATGTAAACAGATTTAATGTTG CTATTACCAG AG CAAAAG TAG G CATACTTTG CATAATGTCTG ATAG
AG A CCTTTATG
ACAAGTT G CAATTTA CAAG T CTT G AAATTCCA C G TA G GAATGTG G C AA CTTTACAAG CTG
AAAAT GTAAC AG G ACT CTTTA
AAG ATTG TAG TAA G GTAATCACTG G G TTACATCCTACACAG G CACCTA CACA CCT CAG TG TTG
AC ACTAAATT CAAAACTG
AAG G TTTATG TG TT G ACATACCT G G CATACCTAAG G ACAT G AC CTATAG AAG A CTCAT
CTCTATG ATG G G TTTTAAAATG A
ATTATCAAGTTAATG GTTACCCTAACATGTTTATCACCCGCGAAGAAG CTATAAGACATGTACGTG CATG
GATTG G CTTCG
ATG TCG AG G G GTGTCATG CTACTAG AG AAG CTGTTG GTAC CAATTTACCTTTAC AG
CTAGGTTTTTCTACAG GTGTTAACCT
AG TTG CTG TACCTA CAG GTTATGTTG ATAC ACCTAATAATACAG ATTTTTCCAG AG TTAGTG
CTAAAC CAC CG C CTG G AG AT
CAATTTAAACACCTCATACCACTTATGTACAAAG GACTTCCTTG G AATG TA GTG
CGTATAAAGATTGTACAAATGTTAAGTG
ACACACTTAAAAATCTCTCTG A CAG AG TC G TATTTG TCTTAT G G G CACATG G CTTTG AG TT G
ACATCTATG AAG TATTTT G T
GAAAATAG GACCTG AG CG CAC CTG TT GT CTAT G TG ATAG AC G TG CCACATG CTTTTCCACTG
CTTCAG AC ACTTATG CCTG T
TG G CAT CATTCTATT G G ATTTG ATTA C G TCTATAATCC G TTTATG ATTG AT G TT
CAACAATG GG G TTTTAC AG GTAACCTACA
AAG CAACC ATG AT CTG TATT G TCAA GTCC ATG G TAAT G CACATG TAG CTA G TT G TG
ATG CAATCATGACTAG GTGTCTAG C
TGTC CAC G AGTG CTTTGTTAAG CGTGTTGACTG G ACTATTGAATATCCTATAATTG GTGATGAACTGAAG
ATTAATG CGGC
TT G TAG AAAG GTTCAACACATG GTTGTTAAAG CTG C ATTATTAG C AG ACAAATTC CCAG
TTCTTCAC G ACATTG GTAACCC
TAAAGCTATTAAG TG T G TA C CTCAA G CTG ATG TAG AAT G GAAGTTCTATG ATG CACAG C
CTTG TAG T G ACAAAG CTTATAA
AATAGAAG AATTATTCTATTCTTATG CCACACATTCTG AC AAATT CACAG ATG G TG TAT G
CCTATTTTGG AATTG CAATGTC
GATAGATATCCTG CTAATTCC ATTG TTTG TAG ATTTG ACACTAG AGTG CTATCTAACCTTAACTTG
CCTG G TT G TG ATG GTG
G C AG TTTG TATG T AAATAA ACATG CATTCCACACACCAG CTTTTGATAAAAGTG
CTTTTGTTAATTTAAAACAATTACCATTT
TT CTATTACTCTG AC AG TC CATG TG AG TCTC ATG G AAAA C AA G TAG TG TCAG
ATATAGATTATGTACCACTAAAGTCTG CIA
CGTGTATAACACGTTG CAATTTAG GTG G TG C TG T CTG TAG ACAT CATG CTAATG AG TACAG
ATTGTATCTCG AT G CTTATAA
CAT G AT G ATCTCA G CTG G CTTTAG CTTGTG G GTTTACAAACAATTTG ATACTTATAACCTCTG G
A ACA CTTTTA CAAG ACTTC
AGAGTTTAGAAAATGTG GCTTTTAATGTTGTAAATAAG G GACACTTTGATG G ACAACAG G
GTGAAGTACCAGTTTCTATCA
TTAATAACACTGTTTACACAAAAGTTG ATG GTGTTG ATG TAG AATTG TTTG
AAAATAAAACAACATTACCTGTTAATGTAG C
ATTTG AG CTTTG G GCTAAG CG CAACATTAAACC AG TAC CA G AG GTG AAAATACTCAATAATTTG
G GTGTG GACATTG CTG C
TAATACTGTG ATCTG G G ACTACAAAAG AG ATG CTCCAG CACATATAT CTACTATT G G TG TTT G
TT CTATG ACTG ACATAG CC
AAG AAACCAACTG A AAC G ATTTG TG CACCACTCACTG TCTTTTTTG AT G G TAG A G TTG AT G
G T CAAG TAG ACTTATTTAG A
AATG CCCGTAATG GTGTTCTTATTACAGAAG GTAGTGTTAAAG G TTTA CAACCAT CTG TAG
GTCCCAAACAAG CTAGTCTT
AATG G AG TCAC ATTAATTG G AG AAG C CG TAAAAACACAG TTC AATTATTATAAG AAAG TT G
ATG GTGTTGTCCAACAATTA
CCTG AAACTTACTTTACTCAG AG TAG AAATTTA CAA G AATTTAAAC CCAG G AGTCAAATG
GAAATTGATTTCTTAG AATTAG
CTATG G ATGAATTCATTG AACG GTATAAATTAGAAG G CTATG CCTTCG AA CATATC GTTTATG G AG
ATTTTAG TC ATAG TCA
G TTAG G TG G TTTA CAT CTACTG ATTG GACTAGCTAAACGTTTTAAG GAATCACCTTTTGAATTAG
AAGATTTTATTCCTATG
G AC AG TA CAG TTAAAAA CTATTTCATAACAG ATG CG C AAA CAG
GTTCATCTAAGTGTGTGTGTTCTGTTATTGATTTATTAC
TT G ATG ATTTTGTTG AAATAATAAAATCCCAAG ATTTATCT G TAG TTT CTAAG G TT G TCAAAG
TG ACTATT G ACTATAC AG A
AATTTCATTTATG CTTTG G TG TAAAG AT G G C CATG TAG AAACATTTTACCCAAAATTACAATCTA G
TCAAG CGTG G CAACCG
G GTGTTG CTATG CCTAATCTTTACAAAATG CAAAG AATG CTATTAG AAAAG TG TG A CCTT
CAAAATTATG GTG ATAGTG CA
ACATTACCTAAAG GCATAATG ATGAATGTCG CAAAATATACTC AACTG TG T CAATATTTAAACACATTAAC
ATTAG CTGTAC
CCTATAATATG AG AG TTATAC ATTTTG GTG CTG GTTCTG ATAAAG G AG TTG CACCAG GTAC AG
CTGTTTTAAG AC AGTG GT
TG CCTAC G G GTACG CTG CTTG T C G ATTCA G ATCTTAAT G ACTTTG TCTCTG AT G CAG
ATTCAACTTTGATTG GTGATTGTG C
AACTGTACATACAG CTAATAAATG G G AT CTCATTATTAG TG ATAT G TA C G ACCCTAA G AC
TAAAAATG TTACAAAAG AAAA
TG ACT CTAAAG AG G GTTTTTTCACTTACATTTGTG G GTTTATACAACAAAAGCTAG CT CTTG GAG
GTTCCGTG G CTATAAAG
ATAACAGAACATTCTTG GAATG CT G ATCTTTATAAG CTCATG G GACACTTCG CATG GTG GACAG
CCTTT G TTACTAATG TG A
ATG C GT CATC ATCTG AAG CATTTTTAATTG GATGTAATTATCTTG G C AAACC AC G C G
AACAAATAG ATG G TTATG TCATG CA
TG CAAATTACATATTTTG GAG G AATACAAAT CCAATTCAG TT G TCTT CCTATTCTTTATTTG ACAT G
AG TAAATTT CCCCTTA
AATTAAG G G GTACTG CTGTTATGTCTTTAAAAGAAG GTCAAATCAATGATATG ATTTTAT CT CTT
CTTAG TAAAG GTAG ACT
TATAATTAG A G AAAACAA CAG AG
TTGTTATTTCTAGTGATGTTCTTGTTAACAACTAAACGAACAATGTTTGTTTTTCTTGTT
TTATTG CCACTAGTCTCTAGTCAGTGTGTTAATCTTACAACCAG AACTCAATTAC CCC CT G CATA
CACTAATTCTTT CAC AC G
TG G TGTTTATTACCCTG ACAAAG TTTTC AG ATC CTCAG TTTTACATT CAACT CAG G
ACTTGTTCTTACCTTTCTTTTCCAATGT
TA CTTG G TTCCATG CTATACATGTCTCTG G GACCAATG G TA CTAA G AG GTTTG CTAA
CCCTGTCCTACCATTTAATGATG GT
GTTTATTTTG CTTCCACTG AG AAG TCTAACATAATAAG AG G CTG GATTTTTGGTACTACTTTAG ATTCG
AAG AC CCAGTCCC
TACTTATTGTTAATAACG CTACTAATG TT GTTATTAAAGTCTGTG AATTTCAATTTTG TAATG
ATCCATTTTTG G GTGTTTATT
ACC ACAAAAACAACAAAAG TTG G AT G G AAA GTG A G TTC AG AG TTTATTCTA G TG CG
AATAATTG CACTTTTGAATATGTCT
CT CA G CCTTTTCTTATG GACCTTG AAG G AAAAC AG G G TAATTTCAAAAATCTTAG GGAATTTG
TGTTTAAGAATATTG ATG

GTTATTTTAAAATATATTCTAAG CAC ACG CCTATTAATTTAGTG CGTG GTCTCCCTCAG GGTTTTTCG G
CTTTAG AACCATTG
GTAGATTTG CCAATAG GTATTAACATCACTAG GTTTCAAANNNNNN CTTTACATAGAAGTTATTTGACTCCTG
GTGATTCTT
CTTCAG GTTG GACAG CTG GTG CTG CAGCTTATTATGTG G GTTATCTTCAACCTAG GA
CTTTTCTATTAAAATATAAT G AAA
ATG GAACCATTACAGATG CTG TAG ACTGTG CACTTG ACCCTCTCTCAG
AAACAAAGTGTACGTTGAAATCCTTCACTGTAG
AAAAAG
GAATCTATCAAACTTCTAACTTTAGAGTCCAACCAACAGAATCTATTGTTAGATTTCCTAATATTACAAACTTGTG
CCCTTTTG GTGAAGTTTTTAACG C CA CCAG ATTTG CAT CTG TTTAT G CTTGG AACAG GAAG AG
AATCAG CAA CTG TGTT G CT
GATTATTCTGTCCTATATAATTCCG CATCATTTTCCACTTTTAAGTGTTATG G
AGTGTCTCCTACTAAATTAAATGATCTCTG C
TTTACTAATGTCTATG CA G ATTCATTTG TAATTAG AG GTG ATGAAGTC AG A CAA ATCG CTCCAG
GG CAAACTG GAAATATT
G CTGATTATAATTATAAATTACCAGATGATTTTACAG G CTG CGTTATAG CTTG
GAATTCTAACAATCTTGATTCTAAG GTTG
GTG GTAATTATAATTACCTGTATAGATTGTTTAG G AAGTCTAATCTC AAACCTTTTG AG AG AG
ATATTTCAACTG AAATCTA
TCAG GCCGGTAG CACACCTTGTAATG GTGTTAAAG GTTTTAATTGTTACTTTCCTTTACAATCATATG
GTTTCCAACCCACTT
ATG GTGTTG GTTA CCAACC ATA CA G AGTAGTAGTACTTTCTTTTGAACTTCTACATG CA CCAG
CAACTGTTTGTG GACCTAA
AAAGTCTACTAATTTG GTTAAAAACAAATGTGTCAATTTCAACTTCAATG GTTTAACAG G CAC AG GT GTT
CTTACTG AG T CT
AACAAAAAGTTTCTG CCTTTC CAACAATTTG G CAG AG AC ATTG CT G ACACTACTG AT G CT GTCC
GTG ATCCAC AG ACA CTTG
AGATTCTTGACATTACACCATGTTCTTTTGGTG GTGTCAGTGTTATAACACCAG GAACAAATACTTCTAACCAG
GTTG CTGT
TCTTTATCAGG GTGTTAACTG CACAG AAGTCCCTGTTG CTATTCATG CAGATCAACTTACTCCTACTTG G
CGTGTTTATTCTA
CAG GTTCTAATGTTTTTCAAACACGTG CAG G CTGTTTAATAG G G G CTG AACATGTCAACAACTCATATG
AGTGTG ACATAC
CCATTG G TG CAG GTATATG CG CTAGTTATCAGACTCAG AC TAATT CTC CTCG GCGGG CACG TAG
TGTAGCTAG TCAATCCA
TCATTG CCTACACTATGT CA CTTG GTG TAG AAAATTCA GTTG CTTACTCTAATAACTCTATTG CC
ATAC C CA CAAATTTTA CT
ATTAGTG TTACCACAG AAATTCTACCAGTGTCTATG ACC AAG AC ATCA G TAG ATTGT ACAAT G TAC
ATTTG TG G TG ATTC AA
CTG AATG CAG CAATCTTTTGTTG CAATATG G CAGTTTTTGTACACAATTAAAC CGTG CTTTAACTG
GAATAG CT GTT G AACA
AGA CAAAAA CACCC AAG AAGTTTTTG CACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTG
GTG GTTTTAA
TTTTTC ACAAAT ATTAC CAG AT CCAT CAAAAC CAAG CAAGAG GTCATTTATTG AAG ATCTACTTTTC
AAC AAA GTG A CACTT
G CAGATG CTG G CTTCATCAAACAATATG GTGATTG CCTTG GTG ATATTG CTG CTAG AG
ACCTCATTTGTG CACAAAAGTTT
AACG G CCTTACTGTTTTG CCACCTTTG CTCAC AG ATGAAATG ATTG CTCAATACACTTCTG
CACTGTTAG CG G GTACAATCA
CTTCTG GTTG G AC CTTTG GTG C AG GT G CTG CATTACAAATACCATTTG CTATG CAAATG G
CTTATAG GTTTAATG GTATTG G
AGTTACAC AG AATGTT CTCTATG AG AACCAAAAATTGATTGCCAACCAATTTAATAGTG CTATTG G
CAAAATTCAAGACTCA
CTTTCTTCCACAG CAAGTGCACTTGG AAAACTTCAAG ATGTG GTCAACCAAAATG CACAAG CTTTAAACACG
CTTGTTAAAC
AACTTAG CTCCAATTTTG GT G CAATTTC AAGTG TTTTAAAT G ATAT CCTTTCAC GTCTTG AC
AAAGTTG AG G CTG AAGTG CA
AATT G AT AG GTTG AT CACAG G CAGACTTCAAAGTTTG CAGACATATGTGACTCAACAATTAATTAG AG
CT G CAG AAATC A G
AG CTTCT G CTAATCTTG CT G CTA CTAAAATGTC AG AG TG TG TACTTG G ACAATCAAAAAG AG
TTG ATTTTT GTG GAAAG G G
CTATCATCTTATGTC CTTC C CTC AGTC AG CAC CTCAT G GTGTAGTCTTCTTG CAT GTG
ACTTATGTCCCTG CACAAGAAAA G A
ACTTCACAACTG CTCCTG CCATTTGTCATG ATG G AAAAG CAC ACTTTCCTCGTG AAG
GTGTCTTTGTTTCAAATG G CAC ACA
CTG GTTTGTAACACAAAG G AATTTTTAT G AACC ACAAAT CATTACTAC AG A C AA CACATTTG TGT
CTG GTAACTGTG ATG TT
GTAATAG GAATTGTCAACAACACAGTTTATG ATCCTTTG CAACCTGAATTAG ACTCATTCAAG GAG
GAGTTAGATAAATAT
TTTAAG A ATCATACATC ACCAG ATGTTGATTTAG GT G ACATCTCTGG CATTAATG
CTTCAGTTGTAAACATTCAAAAAGAAA
TT G ACCG CCTCAATG A G GTTG C CAAGAATTTAAATG AATCTCTCATCG AT CTCC AAG AACTTG
GAAAGTATG AG CA GTATA
TAAAATG G CCATG GTACATTTG G CTAG GTTTTATAG CTG G CTTGATTG CC ATAG TAATG GTG
ACAATTATG CTTTG CTG TAT
G AC CAGTTG CTGTAGTTGTCTCAAG GG CTGTTGTTCTTG TG G ATCCTG CTG CAAATTTG ATG AAG
AC G A CTCTG AG CC AG T
G CTCAAAG GAG TCAAATTACATTAC ACATAA ACG AA CTTAT G G ATTTGTTTATG AG AATCTTCAC
AATT G GAACTGTAACTT
TG AAGCAAG GTGAAATCAAG GATG CTACTCCTTCAGATTTTGTTCG CG CTACTG CAACG
ATACCGATACAAGC CTCACTCC
CTTTCG GATG GCTTATTGTTG G CGTTG CA CTTCTTG CTGTTTTTCATAG CG CTTCCAAAATCATAACCC
TCAAAAAG AG ATG
G CAACTAG CACTCTCCAAG GGTGTTCACTTTGTTTG
CAACTTGCTGTTGTTGTTTGTAACAGTTTACTCACACCTTTTG CTCG
TTG CTG CTG G CCTTGAAG CCCCTTTTCTCTATCTTTATG CTTTAGTCTACTTCTTG CAG AG
TATAAACTTTGTAAG AATAATA
ATG AGG CTTTGG CTTTG CTG GAAATG CCG TT CC AAAAAC C CATTACTTTATG ATG
CCAACTATTTTCTTTG CTG G CATACTAA
TTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTGTCATTACTTTAG GTGATGG
CACAACAAGTCCTATTT
CTG AACATGACTACCAGATTG GTG GTTATACTGAAAAATG G G AATCTGG AG TAAAAG
ACTGTGTTGTATTACACAGTTACT
TCA CTTC AG ACTATTAC CAG CTGTACTCAACTCAATTG AG TACAG ACACTG
GTGTTGAACATGTTACCTTCTTCATCTACAAT
AAAATTGTTG ATG AG CCTG AAG AACATGT CCAAATTC A CACAAT CG AC G GTTCATCCG G AGTTG
TTAATCCA GTAAT G G AA
CCAATTTATG ATG AACCG A CG ACG ACTACTAG CGTG CCTTTGTAAG CACAAG CTG ATG
AGTACGAACTTATGTACTCATTC
GTTTCG G AAG AG AC AG GTACGTTAATAGTTAATAG CGTACTTCTTTTTCTTG CTTTCGTG GTATTCTTG
CTAG TTA CA CTAG C
CAT C CTTACTG CGCTTCG ATTGTGTG CGTACTG CTG CAATATT G TTAAC G T G AG TCTTG
TAAAACCTT CTTTTTAC G TTTACT
CTCGTGTTAAAAATCTGAATTCTTCTAG AG TT CTTG AT CTTCTG GT CTA AAC G AA
CTAAATATTATATTAG TTTTTCTGTTTG G
AACTTTAATTTTAG C CATG G CAG ATTC CAA CG G TACTATTACC G TTG AAG AG CTTAAAAAG
CTCCTTGAACAATG G AA C CTA
GTAATAG GTTTCCTATTC CTTACATG G ATTTGTCTTCTACAATTTG CCTATG CCAACAG G AATAG
GTTTTTGTATATAATTAA

GTTAATTTTCCTCTGGCTGTTATGGCCAGTAACTTTAGCTTGTTTTGTGCTTGCTGCTGTTTACAGAATAAATTG
GATCACCG
GTGGAATTGCTATCGCAATGGCTTGTCTTGTAGGCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTGC
GCG
TACGCGTTCCATGTGGTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATGGCACTATTCTGACCAGA
CCG
CTTCTAGAAAGTG AACTCGTAATCG GAG CTGTGATCCTTCGTG GACATCTTCGTATTG CTG GACAC
CATCTAG G ACG CTGT
GACATCAAG GACCTG CCTAAAG AAATCACTGTTG CTACATCACG AACGCTTTCTTATTACAAATTG G GAG
CTTCG CAG CGT
GTAGCAGGTGACTCAGGTTTTGCTGCATACAGTCGCTACAGGATTGGCAACTATAAATTAAACACAGACCATTCCAGTA
GC
AGTGACAATATTGCTTTGCTTGTACAGTAAGCGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAGCAGAG
ATA
TTACTAATTATTATGAGGACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTAT
CTAA
GTCACTAACTGAGAATAAATATTCTCAATTAGATGAAGAGCAACCAATG GAG ATTG
ATTAAACGAACATGAAAATTATTCT
TTTCTT G G CACTGATAACACTCG CTACTTGTGAGCTTTATCACTACCAAGAGTGTG TTAG AG
GTACAACAGTACTTTTAAAA
GAACCTTGCTCTTCTGGAACATACGAGGGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTGCACTGACTTGCT
TTA
GCACTCAATTTGCTTTTG CTTGTCCT GACG G CGTAAAACACGTCTATCAGTTACGTG CC
AGATCAGTTTCACCTAAACTGTTC
ATCAGACAAGAGGAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCGGCAATAGTGTTTATAACACTTTGCT
TCAC
ACTCAAAAGAAAGACAGAATGATTGAACTTTCATTAATTG
ACTTCTATTTGTGCTTTTTAGCCTTTCTGCTATTCCTTGTTTTA
ATTATGCTTATTATCTTTTGGTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACGCCTAAACGAACATGAAAT
TTCT
TGTTTTCTTAGGAATCATCACAACTGTAGCTGCATTTCACCAAGAATGTAGTTTACAGTCATGTACTCAACATCAACCA
TAT
GTAGTTG ATGACCCGTGTCCTATTCACTTCTATTCTAAATG GTATATTAGAGTAG GAG CTAGAAAATCAG
CACCTTTAATTG
AATTGTG
CGTGGATGAGGCTGGTTCTAAATCACCCATTCAGTACATCGATATCGGTAATTATACAGTTTCCTGTTTACCTTTT
ACAATTAATTGCCAGGAACCTAAATTGGGTAGTCTTGTAGTGCGTTGTTCGTTCTATGAAGACTTTTTAGAGTATCATG
ACG
TTCGTGTTGTTTTAGATTTTATCTAAACGAACAAACTAAAATGTCTGATAATGGACCCCAAAATCAGCGAAATGCACCC
CGC
ATTACGTTTGGTGGACCCTCAGATTCAACTGGCAGTAACCAGAATG GAG AACG CAGTG G G G CG CG
ATCAAAACAACGTCG
GCCCCAAGGTTTACCCAATAATACTGCGTCTTGGTTCACCGCTCTCACTCAACATGGCAAGGAAGACCTTAAATTCCCT
CGA
GGACAAGGCGTTCCAATTAACACCAATAGCAGTCCAGATGACCAAATTGG CTACTACCG AAG AG CTACCAG
ACGAATTCG
TG GTG GTGACG GTAAAATGAAAG ATCTCAGTCCAAG ATG GTATTTCTACTACCTAG G AACTG G GC
CAG AAG CTG GACTT
CCCTATG GTG CTAACAAAGACG G CATCATATG G GTTG CAACTGAG G GAG CCTTGAATACACC AAAAG
ATCACATTG GCAC
CCGCAATCCTGCTAACAATGCTGCAATCGTGCTACAACTTCCTCAAGGAACAACATTGCCAAAAGGCTTCTACGCAGAA
GG
GAG CAGAG G CG G CAGTCAAG CCTCTTCTCGTTCCTCATCACGTAGTCG
CAACAGTTCAAGAAATTCAACTCCAG G C AG CAG
TAG G G G AATTTCTCCTG CTAGAATG G CT G G CAATG GCG GTGATG CTG CTCTTG CTTTG CTG
CTG CTTG ACAGATTGAACCA
GCTTGAGAGCAAAATGTCTGGTAAAGGCCAACAACAACAAGGCCAAACTGTCACTAAGAAATCTGCTGCTGAGGCTTCT
A
AGAAGCCTCGGCAAAAACGTACTGCCACTAAAGCATACAATGTAACACAAGCTTTCGGCAGACGTGGTCCAGAACAAAC
C
CAAGGAAATTTTGGGGACCAGGAACTAATCAGACAAGGAACTGATTACAAACATTGG
CCGCAAATTGCACAATTTGCCCC
CAGCGCTTCAGCGTTCTTCGGAATGTCG CGCATTGGCATGGAAGTCACACCTTCG
GGAACGTGGTTGACCTACACAGGTG
CCATCAAATTGGATGACAAAGATCCAAATTTCAAAGATCAAGTCATTTTGCTGAATAAGCATATTGACGCATACAAAAC
ATT
CCCACCAACAGAGCCTAAAAAGGACAAAAAGAAGAAGGCTGATGAAACTCAAGCCTTACCGCAGAGACAGAAGAAACAG

CAAACTGTGACTCTTCTTCCTG CTG CAGATTTG GATGATTTCTCCAAACAATTG CAACAATCCATG AG
CAGTGCTGACTCAA
CTCAGGCCTAAACTCATGCAGACCACACAAGGCAGATGGGCTATATAAACGTTTTCGCTTTTCCGTTTACGATATATAG
TCT
ACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACAAGTAGATGTAGTTAACTTTAATCTCACATAGCAATCTTTA
ATC
AGTGTGTAACATTAG G GAG G ACTTG AAAGAGCCACCACATTTTCACCGAG
GCCACGCGGAGTACGATCGAGTGTACAGTG
AACAATGCTAGGGAGAGCTGCCTATATGGAAGAGCCCTAATGTGTAAAATTAATTTTAGTAGTGCTATCCCCATGNNNN
N
NNNNNNNNNNNNNNNNNNNNNNN NAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
SEQ ID NO: 19 >SA_P2_gp02 surface glycoprote in, from gen ome accession SA_P2_t0.9_q20 M FVF LVLLP LVSSQCVN LTTRTQLP PAYTNSFTRGVYYPDKVF RSSVLHSTQDLF LP FFSNVTWF HAI
HVSGTNGTK RFAN PVLP F
NDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNDPFLGVYYHKNNKSWM
ESEFRVYSSANNCTFEYV
SQP F LM D LEG KQG NFKN LR EFV FKN I DGYFKIYSKIATP I NLVRG LPQG FSAL E P LVDL
PI G I NITRFQXXXLHRSYLTPG DSSSGVVT
AGAAAYYVGYLQP RTF LLKYN ENGTITDAVDCALDP LSETKCTL KSFTVE KG IYQTSNF RVQPTESIVRF
PN ITN LCP FG EVF NAIR
FASVYAW N RKR ISNCVADYSVLYNSASFSTF KCYGVSPTKLN DLCFTNVYADSFVIRG DEVRQIAPGQTG N
IADYNYKLPDDFTG
CVIAWNSN N LDSKVGG NYNYLYRLF RKSN LKPFE RDIST EIYQAGSTPCNGVKG F NCYF PLQSYG
FQPTYGVGYQPYRVVVLSF E
LLHAPATVCGPKKSTN LVKN KCVN FN ENG LTGTGVLTESN KKF LP FQQFG RD IADTTDAVR D PQTL
El LD ITPCSF G GVSVITP GT
NTSNQVAVLYQGVNCTEVPVAI HADQLTPTW RVYSTGSNVFOTRAGCLIGAEHVN NSYEC DI PI GAG I
CASYQTQTNSP R RARS
VASQSI IAYTMSLGVENSVAYSN NSIAI PTN FTISVTTE I LPVSMTKTSVDCTMYICG DSTECSN
LLLQYGSFCTQLNRALTG IAVEQ
DKNTQEVFAQVKQIYKTP PI KDFGG F NFSQILP DPSKPSKRSF I E DLLF N KVTLADAG Fl KQYG
DCLG DIAAR DL I CAQKF NG LTVL
P P L LTD EM IAQYTSALLAGTITSGWTFGAGAALQI P FAM QM AYR FNG I GVTQNVLYE N QKL
IANQF NSAIG KIQDSLSSTASALG
KLQDVVNQNAQALNTLVKQLSSN FGAISSVLN DILSR LDKVEAEVQI DRLITG R LQSLQTYVTQQL I
RAAE I RASAN LAATKMSEC

VLGQSKRVDFCGKGYH LMSFPQSAPHGVVFLHVTYVPAQEKNFTTAPAICHDG
KAHFPREGVFVSNGTHWFVTQRNFYEPQII
TTDNTFVSG
NCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAKNLNESLI
DLQE

PVLKGVKLHYT
SEQ ID NO: 20 >MW520923.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/hunnan/USA/M N-M DH-2399/2021, complete genome, example of Brazilian P1 lineage.
CAACTTTCGATCTCTTGTAG ATCTGTTCTCTAAACGAACTTTAAAATCTGTGTG G CTGTCACTCGGCTGCATG
CTTAGTG
CACTCACG CAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTG CAGG
CTGCTTA
CGGTTTCGTCCGTGTTG CAGCCGATCATCAG CACATCTAG GTTTTGTCCGG GTGTGACCGAAAG GTAAGATG
GAGAGCCT
TGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTG
CCTGTTTTACAGGTTCGCGACGTGCTCGTACGTGG CT
TTG GAG ACTCCGTG GAG GAG GTCTTATCAGAG G CACGTCAACATCTTAAAGAT G G CACTTGTG G
CTTAGTAGAAGTTGAA
AAAG G CGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCG GATG CTCGAACTGCACCTCATG
GTCATGT
TATG GTTGAG CTGGTAGCAGAACTCGAAG GCATTCAGTACG
GTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATG
TG GGCGAAATACCAGTG GCTTACCGCAAGGTTCTTCTTCGTAAGAACGGTAATAAAG GAG
CTGGTGGCCATAGTTACGGC
GCCGATCTAAAGTCATTTGACTTAGGCG ACG AGCTTGGCACTGATCCTTATGAAGACTTTCAAGAAAACTG
GAACACTAA
ACATAGCAGTGGTGTTACCCGTGAACTCATG CGTGAG CTTAACG GAG
GGGCATACACTCGCTATGTCGATAACAACTTCT
GTGGCCCTGATGGCTACCCTCTTGAGTG CATTAAAGACCTTCTAG CACGTG CTG GTAAAG CTTCATG
CACTTTGTCCG AA
CAACTGGACTTTATTGACACTAAGAGGGGTGTATACTGCTG CCGTGAACATGAG CATGAAATTGCTTGGTACACG
GAACG
TTCTGAAAAGAG CTATGAATTG CAGACACCTTTTGAAATTAAATTG GCAAAGAAATTTGACACCTTCAATGG
GGAATGTC
CAAATTTTGTATTTCCCTTAAATTCCATAATCAAG ACTATTCAACCAAG G GTTGAAAAGAAAAAG CTTGATGG
CTTTATG
G GTAGAATTCGATCTGTCTATCCAGTTG CGTCACCAAATGAATGCAACCAAATGTG
CCTTTCAACTCTCATGAAGTGTGA
TCATTGTGGTGAAACTTCATGG CAGACGGGCGATTTTGTTAAAGCCACTTG CGAATTTTGTGG
CACTGAGAATTTG ACTA
AAG AAG GTGCCACTACTTGTG GTTACTTACCCCAAAATG CTGTTGTTAAAATTTATTGTCCA G
CATGTCACAATTCAGAA
GTAG GACCTG AG CATAGTCTTG CCGAATACCATAATGAATCTG GCTTGAAAACCATTCTTCGTAAGGGTG
GTCGCACTAT
TG CCTTTGGAGGCTGTGTGTTCTCTTATGTTG GTTGCCATAACAAGTGTGCCTATTG GGTTCCACGTG CTAG
CGCTAACA
TAG GTTGTAACCATAC AG GTGTTGTTG G
AGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAG
AAAGTCAACATCAATATTGTTG GTG ACTTTAAACTTAATGAAGAGATCGCCATTATTTTG
GCATCTTTTTCTGCTTCCAC
AAGTGCTTTTGTG GAAACTGTG
AAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAG
TTACAAAAG GAAAAGCTAAAAAAG GTG CCTG GAATATTG GTGAACAGAAATCAATACTGAGTCCTCTTTATG
CATTTG CA
TCAGAGG CTG CTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTG
CGTGTTTTACAG AA
GG CCG
CTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTTGG
CTACTAACAATCTAGTTGTAATGGCCTACATTACAG GTG GTGTTGTTCAGTTGACTTCG
CAGTGGCTAACTAACATCTTT
GG CACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAG GTGTAGAGTTTCTTA
GAGA
CGGTTG GGAAATTGTTAAATTTATCTCAACCTGTG CTTGTGAAATTGTCGGTGG
ACAAATTGTCACCTGTGCAAAG GAAA
TTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTGG CTTTGTGTG
CTGACTCTATCATTATTGGTG G A
GCTAAACTTAAAG CCTTGAATTTAG GTGAAACATTTGTCACGCACTCAAAGG
GATTGTACAGAAAGTGTGTTAAATCCAG
AGAAGAAACTG GCCTACTCATG CCTCTAAAAGCCCCAAAAGAAATTATCTTCTTAGAGG
GAGAAACACTTCCCACAGAAG
TGTTAACAGAGGAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAGTGAAGCTGTTGAAGCTCC
A
TTGGTTG GTACACCAGTTTGTATTAACGGG CTTATGTTG
CTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTG CACC
TAATATG ATG GTAACAAACAATACCTTCACACTCAAAGG CG GT G CACCAACAAAG GTTACTTTTG GTG
ATG ATACTGTG A
TAG AAGTG CAAG GTTACAAG AGTGTGAATATCACTTTTGAACTTGATGAAAGG
ATTGATAAAGTACTTAATGAGAAGTG C
TCTG CCTATACAGTTGAACTCG GTACAGAAGTAAATGAGTTCG CCTGTGTTGTG G CAG ATG
CTGTCATAAAAACTTTG CA
ACCAGTATCTGAATTACTTACACCACTGGG CATTGATTTAGATGAGTG
GAGTATGGCTACATACTACTTATTTGATGAGT
CTG GTGAGTTTAAATTGG CTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAG GATGAAGAAGAAG GTG
ATTGTGAA
GAAGAAGAGTTTGAGCCATCAACTCAATATGAGTATGGTACTGAAGATGATTACCAAGGTAAACCTTTG
GAATTTGGTGC
CACTTCTGCTG CTCTTCAACCTGAAGAAGAG
CAAGAAGAAGATTGGTTAGATGATGATAGTCAACAAACTGTTGGTCAAC
AAGACGG CAGTGAGG ACAATCAGACAACTACTATTCAAACAATTGTTG AG GTTCAACCTCAATTAGAGATG
GAACTTACA
CCAGTTGTTCAGACTATTGAAGTGAATAGTTTTAGTG
GTTATTTAAAACTTACTGACAATGTATACATTAAAAATGCAGA
CATTGTG GAAGAAG CTAAAAAG GTAAAACCAACAGTGGTTGTTAATGCAG CCAATGTTTACCTTAAACATG
GAG GAG GTG
TTGCAG GAG CCTTAAATAAG
GCTACTAACAATGCCATGCAAGTTGAATCTGATGATTACATAGCTACTAATGGACCACTT
AAAGTG G GTG GTAGTTGTGTTTTAAG CG G ACACAATCTTG CTAAACACTGTCTTCATGTTGTC G G
CCCAAATGTTAACAA
AGGTGAAGACATTCAACTTCTTAAGAGTGCTTATGAAAATTTTAATCAG
CACGAAGTTCTACTTGCACCATTATTATCAG
CTGGTATTTTTGGTGCTGACCCTATACATTCTTTAAGAGTTTGTGTAGATACTGTTCGCACAAATGTCTACTTAGCTGT
C
TTTGATAAAAATCTCTATGACAAACTTGTTTTAAGCTTTTTG GAAATGAAGAGTGAAAAG
CAAGTTGAACAAAAGATCG C

TG AG ATTCCTAAAG AG GAAG TTAAG CCATTTATAACTG AAAG TAAACCTTCA G TT G AACAG AG
AAAACAAG ATG ATAAG A
AAATCAAAG CTTG TG TTG AA G AAG TTACAA CAACT CT G G AAG AA ACTAA G TTC CTCAC AG
AAAACTT G TTACTTTATATT
GACATTAATG G CAATCTTCATCCAG ATTCTG CC ACTCTTG TTAG T G ACATTG A C
ATCACTTTCTTAAA G AAAG ATG CTCC
ATATATAGTG G GTG ATG TTG TT CAAGAG G GTGTTTTAACTG CTGTG GTTATACCTACTAAAAAG G
CTG GTG G CACTACTG
AAATGCTAG CGAAAGCTTTG AG AAAAGTG CCAACAG ACAATTATATAACCACTTACCCG G GTC AG G
GTTTAAATG GTTAC
ACT G TAG AG G AG G CAAAG ACAGTG CTTAAAAAGTGTAAAAGTG
CCTTTTACATTCTACCATCTATTATCTCTAATG AG AA
G CAAG AAATTCTT G G AA CTG TTTCTTG G AATTTG CGAGAAATG CTTG CACATG CAG
AAGAAACACG CAAATTAATG C CT G
TCTGTGTG G AAACTAAAG CCATAGTTTCAACTATACAGCGTAAATATAAG G G TATTAAAATACAAG AG G
GTGTG GTTG AT
TATG GTG CTAG ATTTTACTTTTAC ACCAG TAAAAC AACTGTAG CG TCACTTAT CAA CA CACTTAACG
ATCTAAATG AAAC
TCTTG TTACAATG CC ACTTG G CTATGTAACACATG G CTTAAATTTG GAAG AAG CT G CTC G
GTATATG AG AT CTCT CAAAG
TG CCAG CTACAGTTTCTGTTTCTTCACCTGATG CTGTTACAG CGTATAATG G TTATCTTACTT
CTTCTTCTAAAACAC CT
G AA G AACATTTTATTG AAACC ATCT CACTT G CT G G TTCCTATAAAG ATTG GTCCTATTCTG
GACAATCTACACAACTAG G
TATA G AATTTCTTAAG AG AG GTGATAAAAGTGTATATTACACTAGTAATCCTAC CAC ATTCCAC CTAG
ATG G TG AA G TTA
TCA C CTTTG ACAATCTTAAG ACACTTCTTTCTTTG AG AG AAG TG AG G A CTATTAAG G TG
TTTACAA CA G TA G ACAA CATT
AACCTCCACACG CAAGTTGTG G ACATGTCAATG AC ATATG GACAACAGTTTG GTCCAACTTATTTG G
ATG GAG CTGATGT
TACTAAAATAAAACCT CATAATTCAC ATG AA G GTAAAACATTTTATGTTTTACCTAATG ATG AC ACTCTA
C GT G TTG AG G
CTTTTG AG TA CTACC ACACAA CTG ATC CTAGTTTT CT G G G TAG G TACATG TC AG
CATTAAATCACACTAAAAAGTG G AAA
TACCCACAAGTTAATG GTTTAACTTCTATTAAATG G GCAGATAACAACTGTTATCTTGCCACTG
CATTGTTAACACTCCA
ACAAATAG A G TTG AAGTTTAATCCACCTGCTCTACAAGATGCTTATTACAG AG C AAG G G CTG GT G
AAG CTG CTAACTTTT
GTG CACTTATCTTAG CCTACTGTAATAAGACAGTAG GTG AGTTAG GTGATGTTAG AG AAACAATG
AGTTACTTGTTTCAA
CAT G CCAATTTAG ATTCTTG CAAAAG AG TCTTG AA C G TG GTGTGTAAAACTTGTG G ACAAC AG
C AG ACAACCCTTAAG G G
TG TAG AAG CTG TTATG TA C ATG G G CA CACTTTCTTATG AACAATTTAAG AAAGGTGTTCAG
ATACCTTGTACGTGTG G TA
AACAAG CTACACAATATCTAGTACAACAG G AG TCACCTTTT G TTATG AT G T C AG CAC CAC CT G
CTC AG TATG AACTTAAG
CAT G GTACATTTACTTGTG CTAG TG AG TACA CTG G TAATTAC CA G TG T G GT CACTATAAA C
ATATAACTT CTAAA G AAAC
TTTGTATTG CATAGACG GTG CTTTACTTACAAAGTCCTCAG AATACAAAG G TCCTATTACG G ATG
TTTTCTACAAAG AAA
ACAGTTACACAACAACCATAAAACC AG TTACTTATAAATTG GATG G TG TTG TTTG TA CAG AAATTG A
CCCTAAGTT G G AC
AATTATTATAAGAAAG ACAATTCTTATTTCACAG AG CAA CCAATT G ATCTTG T ACCAAA CCAACC
ATATC CAAAC G CAAG
CTTCGATAATTTTAAGTTTGTATGTG ATAATATCAAATTTG CTGATGATTTAAAC CAGTTAACTG GTTATAAG
AAA CCTG
CTTCAAG AG AG CTTAAAGTTACATTTTTCCCTGACTTAAATG GTGATGTG GTG G CTATTG
ATTATAAACACTACACACCC
TCTTTTAAGAAAG GAG CTAAATTGTTACATAAACCTATTGTTTG G CAT G TTAACAAT G CAA
CTAATAAAG C CAC G TATAA
ACCAAATACCTG GTGTATACGTTGTCTTTG G AG CACAAAACCG GTTG AAA CATCAAATTC GTTTGATG
TACTG AAG TC AG
AG G AC G CG CAG G GAATG GATAATCTTG CCTG CG AAG AT CTAAAAC CAG TCTCTGAAG AAG
TA G TG G AAAATCCTACCATA
CAG AAAG AC G TTCTTG A G TG TAATG TG AAAACTACC G AAG TTG TAG G AG
ACATTATACTTAAACC AG CAAATAATAGTTT
AAAAATTACAG AA G AG GTTG G CCACACAG ATCTAATG G CTG CTTATG TAG
ACAATTCTAGTCTTACTATTAAGAAACCTA
ATG AATTATCTAGAGTGTTAG GTTTG AAAACCCTTG CTACTCATG GTTTAG CTG CTGTTAATAGTGTC
CCTTG G GATACT
ATAG CTAATTATG CTAAG CCTTTTCTTAACAAAGTTGTTAG TACAACTACTAACATAGTTACACG
GTGTTTAAACCGTGT
TTGTACTAATTATATG
CCTTATTTCTTTACTTTATTGCTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAGAATTA
AAG CATCTATG CCGACTACTATAG CAAAGAATACTGTTAAGAGTGTCGGTAAATTTTGTCTAG AG
GCTTCATTTAATTAT
TT G AAG TCACCTAATTTTT CTAAA CTG ATAAATATTATAATTT G GTTTTTACTATTAAGTGTTTG
CCTAG GTTCTTTAAT
CTA CTCAA CC G CTG CTTTAG GTGTTTTAATGTCTAATTTAG G CATG C CTTCTTACT G TA CTG G
TTAC AG AG AA G G CTATT
TG AACTCTACTAATGTCACTATTG C AA CCTACTG TACT G G TT CTATACCTT G TAG
TGTTTGTCTTAGTG GTTTAGATTCT
TTAG ACA CCTAT CCTT CTTT AG AAA CTATA CAAATTACCATTT CATCTTTTAAATG G GATTTAACTG
CTTTTG G CTTAGT
TG CAG AG TG GTTTTTG G CATATATTCTTTTCACTAG GTTTTTCTATGTACTTGG ATTG G CTG
CAATCATG CAATTGTTTT
TCAG CTATTTTG CAGTACATTTTATTAGTAATTCTTG G CTTATGTG GTTAATAATTAATCTTGTACAAATGG
CCCCGATT
TCAG CTATG GTTAG AATGTACATCTTCTTTG CATCATTTTATTATGTATG GAAAAGTTATG
TGCATGTTGTAG ACG G TT G
TAATTCATCAACTTG TATG ATG T G TTACAAAC G TAATAG AG CAACAAG AG T C G AAT G TAC
AACTATTG TTAAT G GTGTTA
GAAG GTCCTTTTATGTCTATG CTAATG GAG GTAAAG G CTTTTG CAAACTACACAATTG
GAATTGTGTTAATTGTGATACA
TT CTGTG CTG GTAGTACATTTATTAGTGATGAAGTTG CGAGAG ACTTG TCACTAC AG TTTAAAAG
ACCAATAAAT CCTAC
TG ACCA G TCTTCTTACAT C G TTG ATAG T G TTACAG T G AA G AATG G TT C CATC
CATCTTTA CTTT G ATAAA G CT G GTCAAA
AG A CTTAT G AAAG ACATTCTCTCTCTCATTTTGTTAACTTAG ACAACCTG AG AG CTAATAACACTAAAG
GTTCATTG CCT
ATTAATG TTATAGTTTTTG ATG G TAAATCAAA ATG T G AA G AATCATCTG CAAAAT CA G CG
TCTGTTTACTA CA G T CA G CT
TAT G TG T CAA CCTATACTGTTACTAG ATCAG G C ATTAG T G TCT G ATG TTG GTGATAGTG CG
G AAG TT G CAGTTAAAATGT
TT G ATG CTTA C G TTAATAC G TTTTCAT CAACTTTTAAC G TA CC AAT G
GAAAAACTCAAAACACTAGTTG CAACTG CAG AA
G CTG AA CTTG CAAAGAATGTGTCCTTAG ACAATGTCTTATCTACTTTTATTTCAG CAG CTCG G CAAG G
GTTTGTTGATTC
AG ATGTAG AAA CTAAAG ATG TTGTTGAATGTCTTAAATTG TCAC ATCAATCTG ACAT AG AAG
TTACTG G C G ATAGTT G TA

ATAACTATATG CT CACCT ATAACA AAG TTG AAAAC ATG AC ACCCC GTG ACCTTG GTG
CTTGTATTGACTGTAGTG CG CGT
CATATTAATG CG CAG G TAG CAAAAAG TCA CAA CATTG CTTTGATATG G AACGTTAAAG
ATTTCATGTCATTG TCTG AA CA
ACTAC G AAAACAAATAC G TA G TG CTG CTAAAAAG AATAACTTAC CTTTTAAG TTG AC ATG T G
CAACTACTAG ACAAGTTG
TTAATGTTGTAACAACAAAGATAG CACTTAAG G GTG GTAAAATTGTTAATAATTG GTTGAAG
CAGTTAATTAAAGTTACA
CTTGTGTTCCTTTTTGTTG CTG CTATTTTCTATTTAATAACACCTGTTCATGTCATGTCTAAACATACTG
ACTTTTCAAG
TG AAATCATAGG ATACAAG G CTATTGATG GTG GTG TCA CT C GTG ACATAG CAT CTACA G
ATACTTG TTTT G CTAACAAAC
ATG CTG ATTTTG AC ACATG GTTTAG CCAG CGTG GTG G TAG TTATACTAATG AC AAAG C TTG
CCCATTGATTG CTG CA G TC
ATAACAAG AG AAG TG G GTTTTGTCGTGCCTG GTTTG CCTG G CAC G ATATTACG CACAACTAATG
GTGACTTTTTG CATTT
CTTACCTAG AG TTTTTAG TG C AG TTG G TAACATCTGTTACACACCATCAAAACTTATAG AG TA
CACTG ACTTTG CAA CAT
CAG CTTG TGTTTTG G CT G CTG AATGTACAATTTTTAAAG ATG CTTCTG GTAAG
CCAGTACCATATTGTTATGATACCAAT
GTACTAG AAG G TTCTGTTG CTTATGAAAATTTACG CCCTG ACACACGTTATGTG CTCATG GATG G
CTCTATTATTCAATT
TCCTAACACCTACCTTG AAG G TTC TG TTAG AG T G GTAACAACTTTTGATTCTG AGTACTG TA G G
CAC G G CACTTG T G AAA
G AT CAG AAG CTG GTGTTTGTGTATCTACTAGTG GTAG ATG G
GTACTTAACAATGATTATTACAGATCTTTACCAG G AG TT
TT CTGTG GTG TAG ATG CTGTAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTG GTG
CTTTG GACATATC
AG CATCT ATAGTAG CT G GTG GTATTGTAG CTATCGTAGTAACATG CCTTG CCTACTATTTTATG AG
GTTTAG AAG AG CTT
TTG GTGAATACAGTCATGTAGTTG CCTTTAATACTTTACTATTCCTTATGTCATTCACTG TACT CTG TTTAAC
ACCAG TT
TACTCATTCTTACCTG G TG TTTATTCT G TTATTTACTT G TACTTG A CATTTTATCTTACTAATG
ATGTTTCTTTTTTAG C
ACATATTCAGTG G ATG G TT ATG TTCAC ACCTTTAG TACCTTTCT G G ATAA CAATTG
CTTATATCATTTG TATTTCCA CAA
AG C ATTT CTATTG G TTCTTTAG TAATTAC CTAAAG AG AC G TG TAG TCTTTAATG G TG TTTC
CTTTAG TA CTTTTG AA G AA
G CTG CG CTG TG CAC CTTTTTG TTAAATAAA G AAATGTATCTAAAG TTG C G TA G T G ATG TG
CTATTACCTCTTACG CAATA
TAATAG ATACTTAG CTCTTTATAATAAGTACAAGTATTTTAGTG GAG CAATG GATACAACTAG CTA CAG
AG AAG CT G CTT
GTTGTCATCTCG CAAAG G CTCTCAATG ACTTC AG TAACT CA G G TT CTG
ATGTTCTTTACCAACCACCACAAACCTCTATC
ACCTCAG CTGTTTTG CAG A G TG GTTTTAGAAAAATG G CATTCCCATCTG G T AAAG TTG AG G
GTTGTATGGTACAAGTAAC
TTGTG GTACAACTACACTTAACG GTCTTTG G CTTG ATG ACG TAG TTTACTGTC CAAG AC ATG TG
ATCTG CACCTCTG AAG
ACATG CTTAA CC CTAATTAT G AAGATTTACTCATTCGTAAGTCTAATCATAATTTCTTG GTACAG G CTG
G TAATG TT CAA
CTCAG G GTTATTG GACATTCTATG CAAAATTGTGTACTTAAG CTTAAG GTTG ATACAG CCAATCCTAAG
ACAC CTAAG TA
TAAGTTTGTTCG CATTCAACC AG G A CAG ACTTTTTCAG T GTTAG CTTGTTACAATG G TT CACCAT
CTG GTGTTTACCAAT
GTG CTATG AG G CCCAATTTCACTATTAAG G GTTCATTCCTTAATG GTTCATGTG GTAGTGTTG
GTTTTAACATAGATTAT
GACTGTGTCTCTTTTTGTTACATG CAC CATAT G G AATTACC AACTG G AG TTCAT G CTG G CAC AG
ACTTAG AAG GTAACTT
TTATG G ACCTTTTGTTGACAG G CAAACAG CA CAA G CAG CTG GTACG
GACACAACTATTACAGTTAATGTTTTAG CTTG GT
TGTACG CTG CT G TTATAAAT G GAG ACAG GTG G
TTTCTCAATCGATTTACCACAACTCTTAATGACTTTAACCTTGTG G CT
ATGAAGTACAATTATG AACCTCTAACACAAG ACC ATG TTG ACATACTAG GACCTCTTTCTG CTCAAACTG
GAATTGTCGT
TTTAGATATGTGTG CTTCATTAAAAGAATTACTGCAAAATG G TAT G AAT G G AC G TAC CATATTG G
G TAG TG CTTTATTAG
AAG ATGAATTTACACCTTTTG ATGTTGTTAGACAATG CT CAG GTGTTACTTTCCAAAGTG CAGTG AAAAG
AACAATCAAG
G GTACACACCACTGGTTGTTACTCACAATTTTG ACTT CACTTTTAG TTTTAG T CCAG A G TA CTCAAT
G GTCTTTGTTCTT
TTTTTT G TAT G AAAATG CCTTTTTACCTTTTGCTATG G GTATTATTG CTATGTCTG CTTTTG CAATG
AT G TTT G TC AAAC
ATAAGCATG CATTTCTCTGTTTGTTTTTGTTACCTTCTCTTG CCA CTG TAG CTTATTTTAATATG
GTCTATATG CCTG CT
AG TTG G GTG ATG CGTATTATG ACATG GTTG GATATG GTTGATACTAGTTTGAAG
CTAAAAGACTGTGTTATGTATG CAT C
AG CTGTA GTG TTACTAATCCTTATG AC AG CAAG AA CTGT G TAT G ATG ATG GTG CTAGG A G
AG T G TG GACACTTATGAATG
TCTTG A CACTC G TTTATAAA G TTTATTATG G T AAT G CTTTAG AT CAAG CCATTTCCATGTG G
G CT CTTATAATCTCTG TT
ACTTCTAACTACTCAG G TG TAG TTACAACTG TCAT G TTTTTG G C CA G AG G TATT GTTTTTAT
GT G TG TT G AG T ATTG CCC
TATTTTCTTCATAACTG G TAATACA CTTC AG TG TATAATG CTAGTTTATTGTTTCTTAG G
CTATTTTTGTACTTGTTACT
TTG G CCTCTTTTGTTTACTCAAC CG CTACTTTAG ACTG ACT CTTG GTGTTTATG
ATTACTTAGTTTCTACACAG GAG TTT
AG ATATATG AATTCACAG G G ACTACTCC CAC CCAAG AATAG CATAG ATG
CCTTCAAACTCAACATTAAATTGTTG G GT GT
TG GTGG CAAAC CTTG TATC AAAG TA G CCACTG TA CAG TCTAAAAT G TCA G ATG TAAAG TG
CAC ATCA G TAG T CTTA CTCT
CAGTTTTG CAA CAACT CAG AG TAG AATC AT CATCTAAATTGTG GG
CTCAATGTGTCCAGTTACACAATGACATTCTCTTA
G CTAAAG ATACTACTG AAG CCTTTG AAAAAATG G TTT CA CTACTTTCT GTTTTG CTTTCCATG
CAGG GTG CTG TA G ACAT
AAACAAG CTTTGTGAAG AAATG CTG G ACAAC AG GG CAACCTTACAAG CTATAG C CTCAG AG TTTA
G TTCC CTTCCATCAT
ATG CAG CTTTTG CTACTG CT C AAG AAG CTTATG AG CAGG CTGTTG CTAATG GTGATTCTG
AAGTTGTTCTTAAAAAGTTG
AAG AA G TCTTTG AATGTG G CTAAATCTG AATTT G ACC G TG ATG CAG CCATGCAACGTAAGTTG
G AAAA G AT G G CTG ATCA
AG CTATG ACCCAAATGTATAAACAG G CTAGATCTG AG G A CAAG AG G G CAAAAGTTACTAGTG
CTATG CA G ACAATG CUT
TCACTATG CTTAGAAAGTTG G ATAATGATG CACTCAACAACATTATCAACAATG CAA G AG AT G G TTG
TG TTC CCTTG AAC
ATAATAC CTCTTACAAC AG CAG CCAAACTAATG G TTG T CATAC CA G ACTATAA
CACATATAAAAATAC G TG T G ATG G TA C
AACATTTACTTATG CATCAG CATTGTG G G AAATCCAAC AG G TTGTAG AT G CAG ATAGT AAAATTG
TT CAACTTAG T G AAA
TTAG TAT G G A CAATT CACCTAATTTAG CATGG C CTCTTATT G TAAC A G CTTTAAG G G
CCAATTCTG CTGTCAAATTACAG

AATAATG AG CTTAGTC CTGTTG CA CTACG ACAGATGTCTTGTG CT G CC G GTACTACACAAACTG
CTTGCACTGATG ACAA
TG CGTTAGCTTATTACAACACAACAAAG G GAG GTAG G TTTG TA CTT G CACTG TTATCCGATTTACAG
G ATTTGAAATG G G
CTAG ATT CCCTAAG AG TG ATG GAACTG GTACTATCTATACAGAACTG G AACCACCTTG TAG
GTTTGTTACAG ACACACCT
AAAG GTCCTAAAGTGAAGTATTTATACTTTATTAAAG G ATTAAACAAC CTAAATAG AG GTATG GTACTTG
G TAG TTTAG C
TG CCACAG TACG TCTA C AA G CT G G TAAT G CAACAG AAGTG CCTG CC AATTC AACT G
TATTAT CTTT CTG T G CTTTTG CTG
TAG ATG CTG CTAAAG CTTACAAAG ATTATCTAG CTAGTG G G GG ACAACCAATCACTAATTG
TGTTAAGATGTTGTGTACA
CAC ACTG G TACT G GT CAG G CAATAACAGTTACACCG G AA G CCAATATG GATCAAGAATCCTTTG
G TG G T G CAT CG TG TTG
TCTG TA CTG CCGTTG C CACATAG AT CATC CAAAT CCTAAAG G ATTTTGTG ACTTAAAAG
GTAAGTATGTACAAATACCTA
CAA CTTG TG CTAATG A CCCT G TG G G TTTTA CACTTAAAAAC A CAG T CTG TACCG TCTG CG
GTATGTG GAAAG GTTATG GC
TG TAG TTGTG ATCAACTCCG CGAACCCATG CTTCAGTCAG CTGATG CAC AATCG TTTTTAAACG G G
TTTG CG GTGTAAGT
G CAG CCCGTCTTACAC CGTG CG G CACAG G CACTAG TA CTG ATG TCGTATACAG G GCTTTTG
ACATCTACAATGATAAAGT
AG CTGG TTTT G CTAAATTCCTAAAAACTAATTGTTGTCG CTTCCAAG AAAAG G ACGAAG ATG
ACAATTTAATTGATTCTT
ACTTTG TAG TTAAG A G ACACACTTT CT CTAACTA CCAAC ATG AA G AAA C
AATTTATAATTTACTTAAG G ATT G TCC AG CT
GTTG CTAAACATG ACTTCTTTAAG TTTAG AATAG AC G GTGACATG
GTACCACATATATCACGTCAACGTCTTACTAAATA
CAC AATG G CAG AC CTCG TCTAT G CTTTAAG G CATTTTG ATG AA G G TAATTG TG
ATACATTAAAAG AAATACTTG TC ACAT
ACAATTG TTGTGATG ATG ATTATTTCAATAAAAAG G A CTG GTATG ATTTTG TAG AAAACCCAG
ATATATTACG CG TATAC
G CCAACTTAG GTGAACGTGTACG CCAAG CTTTGTTAAAAACAGTACAATTCTGTG ATG CC ATG CGAAATG
CTG GTATTGT
TG GTGTACTGACATTAGATAATCAAGATCTCAATGGTAACTG G TATG ATTTCGGTGATTTCATACAAACCACG
CCAG G TA
GTG G AG TTCCTG TTG TAG ATT CTTATTATT CATTG TTAATG CCTATATTAACCTTGACCAG G
GCTTTAACTG CAG AG TCA
CATGTTG ACACTG ACTTAACAAAG CCTTACATTAAGTG G GATTTGTTAAAATATGACTTCACG G AA G AG
AG GTTAAAACT
CTTTGACCGTTATTTTAAATATTGG G ATCAGACATACCACCCAAATTGTGTTAACTGTTTG GATGACAG ATG
CATTCTG C
ATTGTG C AAACTTTAATG TTTTATTCT CTAC AG TG TTCC C ACTTACAAG TTTTG G ACCACTAG T
G AG AAAAATATTTG TT
GATG G TG TT CCATTTG TAG TTTC AACTG G ATAC CACTT CAG AG AG CTAG
GTGTTGTACATAATCAG G ATGTAAACTTACA
TAG CTCTAGACTTAGTTTTAAG GAATTACTTGTGTATG CTG CTG A CCCTG CTATGCACG CTG CTTCTG
GTAATCTATTAC
TAG ATAAACG CACTACGTG CTTTT CAG TAG CTG CACTTACTAACAATGTTG
CTTTTCAAACTGTCAAACCCG GTAATTTT
AACAAAG A CTTCT ATG ACTTTG CTGTGTCTAAG G GTTTCTTTAAG G AA G GAAGTTCTGTTG
AATTAAAACACTTCTTCTT
TG CT CAG G AT G G TAATG CTG CTATC AG CGATTATG ACTA CTATCG TTATAAT CTACC
AACAAT G TG TG ATATCAG ACAAC
TACTATTTG TAG TTG AAGTTGTTG ATA AG TACTTTG ATTGTTAC GATG GTG G CTGTATTAATG
CTAACCAAGTCATCGTC
AACAACCTAGACAAATCAG CTG GTTTTCCATTTAATAAATG G G GTAAG G
CTAGACTTTATTATGATTCAATG AG TTATG A
G GATCAAG ATG CACTTTTCG CATATACAAAACGTAATGTCATCCCTACTATAACTCAAATGAATCTTAAGTATG
CCATTA
GTG CAAAG AAT AG AG CTCG CACC G TAG CTG G T G TCTCTAT CTG TAG TACTAT G AC
CAATAG A CAG TTTCAT CAAAAATTA
TTGAAATCAATAG CCG CC ACTAG AG GAG CTACTGTAGTAATTG G AACAAG CAAATTCTATG GTG
GTTG G CAC AA CATG TT
AAAAACTG TTTATAG T G ATG TA G AAAACCCT CACCTTAT G GGTTG G GATTATCCTAAATGTGATAG
AG CCATG CCTAACA
TG CTTAG AATTATG G CCTCACTTG TTCTTG CT CG CAAACATACAACG TG TTG TAG CTT G TC
ACACC G TTTCTATAG ATTA
G CTAATG AG TG TG CTCAAGTATTGAGTGAAATGGTCATGTGTG G CG GTTCACTATATGTTAAACCAG
GTG G AACCTCATC
AG G AG AT G CCACAACTG CTTATG CTAATAGTGTTTTTAACATTTGTCAAG CTGTCACG G
CCAATGTTAATG CACTTTTAT
CTACTGATG GTAACAAAATTG CCG ATAAGTATGTCCG CAATTTACAACACAG ACTTTATGAGTGTCTCTATAG
AAATAG A
G AT G TT G ACA CAG ACTTTG TG AATG AG TTTTACG CATATTTG CGTAAACATTTCTCAATG
ATGATACTCTCTGACGATGC
TGTTGTGTGTTTCAATAG CACTTATG CAT CTCAAG GTCTAGTGG CTAG
CATAAAGAACTTTAAGTCAGTTCTTTATTATC
AAAACAATGTTTTTATGTCTG AAG CAAAATGTTG G ACTG AG A CTG A CCTTACTAAA G
GACCTCATGAATTTTG CTCT CAA
CATACAATG CTAG TTAAACAG G GTG ATG ATTATGTG TACCTTCCTTACCCAG ATC CATC AAG
AATCCTAG GG G CC G G CTG
TTTTG TAG ATG ATAT CG TAAAAACA G ATG GTACACTTATGATTGAACG GTTCGTGTCTTTAG
CTATAGATG CTTACCCAC
TTACTAAACATCCTAATCAG G AG TATG CTG AT G TCTTTCATTTG TACTT ACAATA CATAA G AAAG
CTACATGATG AG TTA
ACAG G AC A CATG TTAG A CAT G TATTCTG TTATG CTTACTAATGATAACACTTCAAG GTATTG G
GAACCTG AG TTTTATG A
G G CTATGTACACACCG CATACAGTCTTACAG G CTGTTGG G G CTTGTGTTCTTTG CAATTCACAG ACTT
CATTAA G AT G TG
GTG CTG CAT ACG TAG ACCATTCTTATGTTG TAAATGCTG TTAC G ACCATG TCATAT CAACAT
CACATAAATT AGTCTTG
TCTGTTAATCCGTATGTTTG CAATGCTCCAG G TTGTGATG TCAC AG ATGTG ACTCAACTTTACTTAG GAG
GTATG AG CTA
TTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTG CT AATG GACAAGTTTTTG
GTTTATATAAAAATAC AT
GTGTTG G TAG CGATAATGTTACTGACTTTAATG CAATTG CAACATG TG ACT G G AC AAATG CTG G
TGATTACATTTTAG CT
AACACCTGTACTG AAAG ACT CAAG CTTTTTG CAG CAGAAACG CT CAAAG CTA CT G AG G AG
ACATTTAAACTG T CTTATG G
TATTG CTACTGTACGTGAAGTG CTGTCTG ACAG A GAATTACATCTTICATG G GAAGTTG
GTAAACCTAGACCACCACTTA
ACC G AAATTATG TCTTTACT G GTTATCGTGTAACTAAAAACAGTAAAG TACAAATAG G AG A G TA CA
C CTTTG AAAAAG GT
GACTATG GTG ATG CTG TTG TTTACC G AG GTACAACAACTTACAAATTAAATGTTG GTGATTATTTTGTG
CTG ACATCACA
TAC AG TAATG CC ATTAAG TG CACCTACACTAGTG CCACAAG AG CACTATGTTAGAATTACTG G
CTTATACCCAACACTCA
ATAT CTCA G AT G AG TTTTCTA G CAATG TTG CAAATTATCAAAAG GTTG G TAT G CAAAAG
TATTCTAC ACTC C AG G G ACCA

CCTG GTACTG GTAAG AG T CATTTTG CTATTG G CCTAG CTCTCTACTACCCTTCTG CTC G CATAG
TG TATA CAG CTTG CTC
TCATG CC G CTGTTG ATG C A CTAT G TG AG AAG G CATTAAAATATTTG CCTATAG ATAAATG
TAG TAG AATTATACCTG CAC
GTG CT C G TG TAG ATTG TTTTG ATAAATT CAAAG T G AATT CAACATTAG AA C AGTATG
TCTTTT GTACTG TAAATG CATTG
CCTG AG A CG ACA G C AG ATATAGTTGTCTTTG AT G AAATTTCAATG G CCACAAATTATGATTTG A
G TG TT G T CAATG CCAG
ATTACGTG CTAAG CAC TATG TG TACATTG G C GAC CCTG CT CAATTACCTG CAC CACG CACATTG
CTAACTAAG GG CACAC
TAG AACCAG AATATTTCAATTCAGTGTGTAG ACTTATGAAAACTATAG GTC CAG AC ATG TTCCTC G G
AA CTTG TCG G C GT
TG TC CT G CTG AAATT G TT G ACACTG TG AG T G CTTTG GTTTATGATAATAAG CTTAAAG CA
CATAAA G ACAAATCAG CTCA
ATG CTTTAAAATGTTTTATAAGG GTGTTATCACGCATGATGTTTCATCTG CAATTAACAG G C CAC AAATAG
G CGTG GTAA
GAG AATTCCTTACACG TAA CC CTG CTTG G AG AAAAG CT G TCTTTATTTCA CCTTATAATTCACA G
AATG CTG TAG CCTCA
AAG ATTTTG G G ACTA CCAACT CAAACTG TT G ATT CATCA CAG G G CTCAG AATATG ACTATG
TC ATATTCA CTCAAAC CAC
TG AAACAG CTCACTCTTGTAATGTAAACAGATTTAATGTTG CTATTACCA G AG C AAAAGT AG G
CATACTTTG CATAATGT
CT G ATAG AG AC CTTTATG ACAAGTTG CAATTTACAAGTCTTG AAATTC CAC G TAG GAATGTG G
CAACTTTACAAG CTG AA
AAT G TAAC AG G A CTCTTTAAAG ATTGTAGTAAG GTAATCACTG G GTTAC AT CCTAC ACAG G
CACCTACACACCTCAGTGT
TG ACACTAAATTC AAAACT G AA G G TTTATG T G TTG ACATACCTG G CATACCTAAG G ACATG
ACCTATAGAAGACTCATCT
CTATG AT G G GTTTTAAAATG AATTATCAAGTTAATG GTTACC CTAACATGTTTATCACCCG CGAAGAAG
CTATAAGACAT
G TAC GT G CATG GATTG G CTTCG ATG T C G AG G G GTGTCATG CTACTAG AG AAG CT G
TTG G TAC CAATTTACCTTTAC AG CT
AG G TTTTTCTACAG GTGTTAACCTAGTTG CTGTACCTACAG G TTATG TT G ATACAC CTAATAATACAG
ATTTTTCCA G A G
TTAGTG CTAAACCACCG CCTG G AG ATCAATTTAAACACCTCATAC CACTTATGTACAAAG GACTTCCTTGG
AAT G TAG TG
CGTATAAAGATTGTACAAATGTTAAGTG ACACACTTAAAAATCTCTCT G ACAG AG T C G TATTTG TCTT
ATG G G CAC ATG G
CTTTG AG TTG ACATCTATGAAGTATTTTGTGAAAATAG G ACCTG AG CG CACCTGTTGTCTATGTG ATAG
ACGTG C CAC AT
G CTTTTCCACTG CTTCAG ACACTTATG CCTGTTG G CAT CATTCTATTG G
ATTTGATTACGTCTATAATCCGTTTATG ATT
G AT G TT C AACAATG G G GTTTTACAG GTAACCTACAAAG CAACCATGATCTGTATTGTCAAGTCCATG
GTAATG CACATGT
AG CTAG TTG T G ATG CAATCATG ACTAG GTGTCTAG CT G T C CAC G AG T G CTTTG TTAAG
C G TG TTG A CTG G ACTATTGAAT
ATCCTATAATTG GTG ATGAACTG AAGATTAATG CG G CTTG TAG AAAG GTTCAACACATG
GTTGTTAAAG CTG CATTATTA
G C AG A CAAATTC CCAG TTCTTCAC G ACATTG GTAACCCTAAAG CTATTAAG T G TG TA
CCTCAAG CTG ATG TAG AAT G G AA
G TTCTATG AT G CA CA G CCTTG TAG TG ACAAAG CTTATAAAATAG AA GAATTATTCTATTCTTATG
CCACACATTCTG ACA
AATTCACAGATG GTGTATG CCTATTTTG GAATTG CAATGTCGATAGATATCCTG CTAATTCC ATT G TTTG
TA G ATTTG AC
ACTAG AG TG CTATCTAACCTTAACTTG CCTGGTTGTGATG GTG G CAGTTTG TATGTAAATAAACATG
CATTCCACACACC
AG CTTTTGATAAAAGT G CTTTTG TTAATTTAAAACAATTAC CATTTTTCTATTACTCTG ACAGTCCATG TG
AG TCTCATG
G AAAA CAA G TAG T G TC AG ATATA G ATTATG TACC ACTAAA G TCT G CTAC G TG
TATAACACG TTG CAATTTAG GTGGTG CT
G T CT G TAG AC ATC AT G CTAATG AG TACA G ATTG TAT CTC G ATG CTTATAACATGATG
ATCTCAG CT G GCTTTAG CTTGTG
G GTTTACAAACAATTTGATACTTATAACCTCTG G AA CA CTTTTA CAA G ACTT CAG A G TTTAG AAA
ATG T G G CTTTTAATG
TT G TAAATAA G G GACACTTTGATG GACAACAG G G TG AAG TAC CAG TTTCTATCATTAATAA
CACT G TTT ACACAAAAG TT
GATG GTGTTG ATG TAG AATTG TTTG AAAATAAAACAACATTAC CTGTTAATGTAG CATTT GAG
CTTTGG G CTAAG CG CAA
CATTAAA C CA G TACCA G AG GTGAAAATACTCAATAATTTG G GTGTG G ACATTG CTG
CTAATACTGTGATCTGG GACTACA
AAAG A G AT G CT C CAG CA CATATATCTACTATTG G T G TTTG TT CTAT G ACT G ACATAG
CCAAGAAAC CAA CTG AAAC G ATT
TGTG CACCACT CA CTG TCTTTTTTG ATG GTAG AGTTG ATG GTCAAG TAG ACTTATTTAG AAATG
CCCGTAATG GTGTTCT
TATTACAG AAGGTAGTGTTAAAG GTTTACAACCATCTG TAG G TCCCAAACAAG CTAGTCTTAATG
GAGTCACATTAATTG
GAG AAG CC GTAAAAACACAGTTCAATTATTATAAGAAAGTTGATG
GTGTTGTCCAACAATTACCTGAAACTTACTTTACT
CAG AG TA G AAATTTACAAGAATTTAAACCCAG G AG T CAAAT G GAAATTG ATTTCTTAG AATTAG
CTATGG ATG AATTCAT
TG AACG GTATAAATTAGAAG GCTATG CCTTC GAACATATC GTTTATG GAG
ATTTTAGTCATAGTCAGTTAG GTG GTTTAC
ATCTACTGATTG GACTAG CTAAACGTTTTAAG G AATCACCTTTTG AATTAG AAGATTTTATTCCTATG G
ACA G TAC AG TT
AAAAACTATTTCATAACAG ATG CG CAAACAG G TTCAT CTAAG TG T G TG TG TT CT G TTATT G
ATTTATTACTT G ATG ATTT
TGTTG AAATAATAAAAT CCCAA G ATTTAT CTG T AG TTTCTAAG G TTG T CAAAG TG A CTATTG
ACT ATAC AG AAATTTCAT
TTATG CTTTG GTGTAAAG ATG G CCATGTAG AAACATTTTACCCAAAATTACAATCTAGTCAAG CGTG G
CAACCGGGTGTT
G CTATG CCTAATCTTTACAAAATG CAAAGAATG CTATTAG AAAAGTGTG ACCTTCAAAATTATG GT G
ATAGTG CAACATT
ACCTAAAGG CATAATG AT G AATG TC G CAAAATATACTCAACTG TG T CAATATTTAAA CAC
ATTAACATTAG CTG TA CCCT
ATAATATG AG AG TTATACATTTTG GTG CTG GTTCTG ATAAAG G A G TTG CACC AG G TAC AG
CTGTTTTAA G ACAG TG GTTG
CCTACG G GTACG CTG CTTGTCG ATTCAGATCTTAATG ACTTTGTCTCTGATG C AG ATTCAACTTTG
ATTG GTGATTGTG C
AACTGTACATACAGCTAATAAATG G GATCTCATTATTAGTGATATGTACGACCCTAAG ACTAAAAATG
TTACAAAAG AAA
ATG ACTCTAAAG AG G GTTITTT CA CTTA CATTTG TG G GTTTATACAA CAAAAG CTAG CTCTTG
GAG G TIC CGTG G CTATA
AAG ATAACAGAACATTCTTGGAATG CTG AT CTTTATAAG CTCATG G G ACACTTCG CATG GTG GACAG
CCTTTGTTACTAA
TG TG AAT G C G TCATCATCT G AA G CATTTTTAATTG G ATG TAATTATCTTG G C AAACC AC G
CG AACAAATAGATG GTTATG
TCATG CATG CAAATTACATATTTTG GAG G AATA CAAATC CAATT CAG TTG TCTTCCTATTCTTTATTT
G ACAT G A G TAAA
TTTCCCCTTAAATTAAG G G G TACT G CT G TTAT G TCTTTAAAAG AAG
GTCAAATCAATGATATGATTTTATCTCTTCTTAG

TAAAG G TAG A CTTATAATTAG AG AAAAC AACA G AG TTG TTATTTCTAGTG ATG TTCTT GTTAA
CAACTAAAC G AA CAATG
TTTGTTTTTCTTGTTTTATTG CCACTAGTCTCTAGTCAG TGTGTTAATTTTACAAACAGAACTCAATTACCCTCTG
CATA
CACTAATTCTTTCACACGTG G TG TTTATTACCCTG AC AAAG TTTTC AG ATC CTCAG
TTTTACATTCAACTC AG G ACTT G T
TCTTACCTTTCTTTTCCAATGTTACTTG GTTCCATG CTATACATGTCTCTG GGACCAATG GTACTAAG A G
GTTTGATAAC
CCTGTCCTACCATTTAATGATG GTGTTTATTTTG CTTC CA CTG AG AA GTCTAACATAATAA G AG G
CTG G ATTTTTG GTAC
TACTTTAGATTCGAAG ACCC AG TCC CTACTTATT G TTAATAAC G CTA CTAAT G TT
GTTATTAAAGTCTGTG AATTTCAAT
TTTGTAATTATCCATTTTTG GGTGTTTATTACCACAAAAACAACAAAAGTTG GATG G AAAG TG AG TTC AG
AG TTTATTCT
AG T G CG AATAATTG CACTTTTGAATATGTCTCTCAG CCTTTTCTTATG GACCTTG AA G GAAAACAG G
GTAATTTCAAAAA
TCTTAGTGAATTTGTGTTTAAGAATATTGATG GTTATTTTAAAATATATTCTAAG CAC ACG
CCTATTAATTTAGTG CGTG
ATCTCCCTCAG G GTTTTTCG G CTTTAG AACCATTG G TAG ATTTG CCAATAG GTATTAACATCACTAGG
TTTCAAACTTTA
CTTG CTTTACATAG AA G TTATTTG ACTCCTG GTGATTCTTCTTCAG GTTG GACAG CTG GTG CTG CA
G CTTATTAT G TG G G
TTATCTTCAACCTAG GACTTTTCTATTAAAATATAATG AAAATG G AA CCATTACAG ATG CTG TA G ACT
G TG CACTT G ACC
CTCTCTC AG AAAC AAA G T G TAC G TTG AAATCCTTCA CTG TAG AAAAAG
GAATCTATCAAACTTCTAACTTTAG AG T C CAA
CCAACAGAATCTATTGTTAG ATTT CCTAATATTAC AAA CTTG TG CCCTTTTG GTG AAGTTTTTAACG
CCACCAGATTTG C
ATCTGTTTATG CTTG GAACAG G AAG AG AATCAGCAACTGTGTTG CTG
ATTATTCTGTCCTATATAATTCCG CATCATTTT
CCACTTTTAAGTGTTATG G AG TG TCT C CTACTAAATTAAAT GATCTCTG CTTTACTAATGTCTATG CAG
ATT CATTTG TA
ATTA G AG GTG ATG A AG TC AG ACAAATC G CTCC AG G G CAAACTG G AACGATTG CT G
ATTATAATTATAAATTACCAG ATG A
TTTTACAG G CTG CGTTATAG CTTG G AATTCTAACAATCTTGATTCTAAG GTTG GTG
GTAATTATAATTACCTG TATAG AT
TGTTTAG G AA GTCTAATCT CAAAC CTTTTG AG AG AG ATATTTCAACTGAAATCTATCAG G CCG
GTAG CACACCTTGTAAT
G GTGTTAAAG GTTTTAATTGTTACTTTCCTTTACAATCATATG GTTTCCAACCCACTTATG GTGTTG
GTTACCAACCATA
CAG AG TAGTAG TACTTTCTTTTGAACTTCTACATG CACCAG CAACTGTTTGTG
GACCTAAAAAGTCTACTAATTTG GTTA
AAAACAAATGTGTCAATTTCAACTTCAATG GTTTAACAG G CACAG GTGTTCTTACTG AG TCTAACAAAAAG
TTTCT G CCT
TTCCAACAATTTGG CAG AG ACATTG CTGACACTACTG ATG CTGTCCGTGATCCACAG ACACTTG AG ATT
CTTG ACATTAC
ACC ATG TTCTTTTG G TG GTGTCAGTGTTATAACACCAG G AACAAATACTTCTAATCAG GTTG
CTGTTCTTTATCAG G GTG
TTAACTG CACAG AAG T CCCT G TT G CTATTCATG CAG ATCAACTTACTCCTACTTG G
CGTGTTTATTCTACAG GTTCTAAT
GTTTTTCAAACACGTG CAG GCTGTTTAATAG GG G CTG AATAT G TCAACAACT CATATG AG TG T G
ACATACCCATT G GTG C
AG G TATATG CG CTAGTTATCAG ACT CAG ACTAATTCTCCTCG G CG G G CACGTAGTGTAG
CTAGTCAATCCATCATTG C CT
ACACTATGTCACTTG GTG C AG AAAATTC AG TT G CTTACTCTAATAACTCTATTG
CCATACCCACAAATTTTACTATTAGT
GTTACCACAG AAATT CTACC AG TG TCTATG ACC AAG ACATCAG TAG ATTGTACAATG TACATTTG
TG G TG ATTCAACTG A
ATG CAG CAATCTTTTGTTG CAATATG G CAGTTTTTGTACACAATTAAACC GTG CTTTAACTG GAATAG
CTGTTG AACAAG
ACAAAAACACCCAAG AA G TTTTTG CACAAGTCAAACAAATTTACAAAACACCACCAATTAAAGATTTTG GTG
GTTTTAAT
TTTTCACAAATATTACCAG ATCCATCAAAACCAAG CAAG A G G TCATTTATTG AAG AT CTACTTTT
CAACAAAGTG ACACT
TG CAG AT G CTG G CTTCATCAAACAATATGGTGATTG CCTTGGTGATATTG CTG CTAG AG
ACCTCATTTGTG CACAAAAGT
TTAACG G CCTTACTGTTTTG CCACCTTTG CT CACAG ATG AAATG AUG
CTCAATACACTTCTGCACTGTTAG CG G G TAC A
ATCACTTCTGGTTG G ACCTTTGGTG CAG GTG CTG CATTACAAATACCATTTGCTATG CAAATG G
CTTATAG GTTTAATGG
TATTG G AGTT ACACAG AATGTT CTCTATG AG AACCAAAAATTGATTGCCAACCAATTTAATAGTGCTATTG
G CAAAATTC
AAG ACTCACTTTCTT CC A CAG CAAGTG CACTTG GAAAACTTCAAG ATGTG GTCAACCAAAATG CA
CAAG CTTTAA ACAC G
CTTGTTAAACAACTTAG CTCCAATTTTG GTG CAATTTCAAG TGTTTTAAATG ATATC CTTT CACGTCTTG
ACAAAG TTG A
G G CTGAAGTG CAAATTG ATAG G TTG ATC A CAG G CAGACTTCAAAGTTTG CAG ACATATG TG
ACTC AACAATTAATT AG AG
CTG CAG AAATCA G AG CTTCTG CTAATCTTG CT G CTATTAAAATG TCAG AG T G TG TACTTG G
AC AAT CAAAAAG AGTT G AT
TTTTGTG G AA AG G G CTAT CATCTTATGTCCTTCCCTC AG TC AG CAC CTCATG
GTGTAGTCTTCTTGCATGTGACTTATGT
CCCTG CA C AAG AAAAG AACTTCAC AACTG CT CCT G CCATTTG TCATGATG G AAAAG
CACACTTTCCTCGTGAAG GTGTCT
TT G TTT CAAAT G G CACACACTG GTTTG TAACACAAAG GAATTTTTATGAACCACAAATCATTACTACAG
ACAACACATTT
GTGTCTG GTAACTGTG ATGTTGTAATAG GAATTGTCAACAACACAGTTTATG ATCCTTTG CAACCTG
AATTAGACTCATT
CAA G GAG G AG TTAG ATAAATATTTTAAG A ATCATACATC ACCAG ATG TT G ATTTA G GT G
ACATCTCTG GCATTAATG CTT
CATTTGTAAACATTCAAAAAGAAATTG ACCG CCTCAATG AG GTTG CCAAGAATTTAAATGAATCTCTCATCG
ATCTC CAA
G AA CTTG GAAAGTATG AG CAG TATATAAAATG G CCATG GTACATTTG G CTAG GTTTTATAG CTG
G CTTGATTG CCATAGT
AATG GT G ACAATTAT G CTTTG CTG TATG AC CAG TTG CT G TA G TTG TCTCAAG G G
CTGTTGTTCTTGTG G ATCCTG CT G CA
AATTTG ATG AAG AC G ACTCTG AG CCAGTG CT CAAAG G AG T CAAATTA CATTACAC ATAAA C
G AACTTAT G GATTTGTTTA
TG AG AAT CTT C ACAATT G G AA CTG TAACTTTG AA G CAAG GTG AAATCAAG GATG
CTACTCCTTCAGATTTTGTTCG CG CT
A CTG CAACGATACCGATACAAG CCTCACTCC CTTTCG GATG G CTTATTGTTGG CGTTG CA CTICTTG
CTEITTTICAGAG
CG CTTCC AAAATC ATAACC CTCAAAAAG AG ATG G CAACTAG CACTCTCCAAG G
GTGTTCACTTTGTTTG CAACTTG CT G T
TGTTGTTTGTAACAGTTTACTCACACCTTTTG CTCGTTG CTG CTG G CCTTG AAGC
CCCTTTTCTCTATCTTTATG CTTTA
GTCTACTTCTTG CAG AG TATAAACTTTG TAAG AATAATAATG AG G CTTTG G CTTTG CTG G AAATG
CCGTTCCAAAAACCC
ATTACTTTATG ATG CCAACTATTTTCTTTG CTG G
CATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTT

CTTCAATTGTCATTACTTCAGGTG ATGGCACAACAAGTCCTATTTCTGAACATGACTACCAG ATTG GTG
GTTATACTG AA
AAATGGGAATCTGGAGTAAAAGACTGTGTTGTATTACACAGTTACTTCACTTCAGACTATTACCAG
CTGTACTCAACTCA
ATTGAGTACAGACACTGGTGTTGAACATGTTACCTTCTTCATCTACAATAAAATTGTTG ATG AG CCTG
AAGAACATGTCC
AAATTCACACAATCGACGGTTCACCCGG AG TTGTTAATC CAGTAATGGAACCAATTTATG
ATGAACCGACGACGACTACT
AGCGTG CCTTTGTAAGCACAAGCTGATG AGTACG AACTTATG TACT CATTCGTTTCG G AAG AG ACAG
GTACGTTAATAGT
TAATAGCGTACTTCTTTTTCTTG CTTTCGTG GTATTCTTGCTAGTTACACTAGCCATCCTTACTG
CGCTTCGATTGTGTG
CGTACTG CTG
CAATATTGTTAACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCT
TCTAG AG TTCCTG ATCTT CTG GTCTAAACG AACTAAATATTATATTAGTTTTTCTGTTTG
GAACTTTAATTTTAGCCATG
GCAGATTCCAACG GTACTATTACCGTTGAAG AG CTTAAAAAGCTC CTTG AACAATGGAACCTAG TAATAG
GTTTCCTATT
CCTTACATGGATTTGTCTTCTACAATTTG
CCTATGCCAACAGGAATAGGTTTTTGTATATAATTAAGTTAATTTTCCTCT
GG CTGTTATG GCCAGTAACTTTAG CTTGTTTTGTG CTTG CTG CTGTTTACAGAATAAATTG
GATCACCGGTGGAATTG CT
ATCGCAATGGCTTGTCTTGTAG GCTTGATGTGGCTCAGCTACTTCATTGCTTCTTTCAGACTGTTTG
CGCGTACGCGTTC
CATGTG GTCATTCAATCCAGAAACTAACATTCTTCTCAACGTGCCACTCCATG G
CACTATTCTGACCAGACCGCTTCTAG
AAAGTGAACTCGTAATCGGAGCTGTG ATCCTTCGTGGACATCTTCGTATTG CTGGACACCATCTAGGACG
CTGTGACATC
AAG GACCTGCCTAAAGAAATCACTGTTGCTACATCACGAACGCTTTCTTATTACAAATTGG GAG CTTCG CAG
CGTGTAGC
AGGTGACTCAG GTTTTGCTGCATACAGTCGCTACAG
GATTGGCAACTATAAATTAAACACAGACCATTCCAGTAGCAGTG
ACAATATTGCTTTGCTTGTACAGTAAGTGACAACAGATGTTTCATCTCGTTGACTTTCAGGTTACTATAG CAG AG
ATATT
ACTAATTATTATGAGG
ACTTTTAAAGTTTCCATTTGGAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTA
AGTCACTAACTGAGAATAAATATTCTCAATTAG ATG AAG AG CAACC AATG G AG ATTG ATTAAACG
AACATG AAAATTATT
CTTTTCTTGG CACTG ATAACACTCGCTACTTGTG AG CTTTATCACTACCAAG AGTG TGTTAG AG G
TACAACAG TACTTTT
AAAAGAACCTTGCTCTTCTGGAACATACGAG GGCAATTCACCATTTCATCCTCTAGCTGATAACAAATTTG CACTG
ACTT
GCTTTAG CACTCAATTTG
CTTTTGCTTGTCCTGACGGCGTAAAACACGTCTATCAGTTACGTGCCAGATCAGTTTCACCT
AAACTGTTCATCAG ACAAG AG GAAGTTCAAGAACTTTACTCTCCAATTTTTCTTATTGTTGCG
GCAATAGTGTTTATAAC
ACTTTG CTTCACACTCAAAAG AAAGACAGAATGATTGAACTTTCATTAATTGACTTCTATTTGTG CTTTTTAG
CCTTTCT
GCTATTCCTTGTTTTAATTATGCTTATTATCTTTTG GTTCTCACTTGAACTGCAAGATCATAATGAAACTTGTCACG
CCT
AAACGAACATGAAATTTCTTGTTTTCTTAGGAATCATCACAACTGTAGCTG
CATTTCACCAAGAATGTAGTTTACAGTCA
TG TACTCAACATCAAC CATATGTAG TTGATGACCCGTGTC CTATTCACTTCTATTCTAAATG GTATATTAG
AG TAG G AG C
TAG AAAATCAG CACCTTTAATTG AATTGTG CGTG GATG AG
GCTGGTTCTAAATCACCCATTCAGTACATCGATATCG G TA
ATTATACAGTTTCCT GTTTACCTTTTACAATTAATTG CCAGAAAC CTAAATTG G G TAG TCTTGTAGTG
CGTTGTTCGTTC
TATG AAG ACTTTTTAGAGTATCATGACGTTCGTGTTGTTTTAG ATTTCATCTAAAC G
AACAAACAAACTAAAATGTCTG A
TAATGGACCCCAAAATCAGCGAAATGCACCCCGCATTACGTTTG
GTGGACCCTCAGATTCAACTGGCAGTAACCAGAATG
GAG AACG CAGTGGG GCG CGATCAAAACAACGTCGG CCCCAAGGTTTACCCAATAATACTG
CGTCTTGGTTCACCGCTCTC
ACTCAACATG GCAAG GAAG ACCTTAAATTCCCTC G AG G ACAAG G CGTTCCAATTAACACCAATAG CAG
TCG AG ATG ACCA
AATTG G CTACTAC CG AAG AG CTACCAGACGAATTCGTG GIG GTG
ACGGTAAAATGAAAGATCTCAGTCCAAGATG GTATT
TCTACTACCTAG GAACTGG GCCAGAAGCTGGACTTCCCTATGGTGCTAACAAAGACGGCATCATATG
GGTTGCAACTGAG
G G AG C CTTG AATACACCAAAAGATCACATTGG CACCCG CAATCCTG CTAACAATGCTG
CAATCGTGCTACAACTTCCTCA
AGGAACAACATTG CCAAAAG GCTTCTACGCAGAAG G GAG CAGAGGCG GCAGTCAAG
CCTCTTCTCGTTCCTCATCACGTA
GTCGCAACAGTTCAAGAAATTCAACTCCAGG CAGCTCTAAACGAACTTCTCCTGCTAGAATG GCTGG CAATGG
CG GTG AT
GCTGCTCTTG CTTTG CTG CTG CTTGACAGATTGAACCAG CTTGAGAGCAAAATGTCTGGTAAAGG
CCAACAACAACAAGG
CCAAACTGTCACTAAG AAATCTG CTG CTG AG G CTTCTAAGAAG CCTCGG
CAAAAACGTACTGCCACTAAAG CATACAATG
TAACACAAG CTTTCGG CAGACGTG GTCCAGAACAAACCCAAGGAAATTTTGGGGACCAGG
AACTAATCAGACAAGGAACT
GATTACAAACATTGGCCGCAAATTG CACAATTTG CCCCCAGCG CTTCAGCGTTCTTCG GAATGTCG CGCATTG
GCATG GA
AGTCACACCTTCG GG AACGTG GTTG AC CTACACAG GTG CCATCAAATTGGATGACAAAG
ATCCAAATTTCAAAGATCAAG
TCATTTTGCTGAATAAG CATATTG AC G CATACAAAACATTCC CACCAACAG AG
CCTAAAAAGGACAAAAAGAAGAAG G CT
GATGAAACTCAAG CCTTACCG CAG AG ACAG AAG AAA CAG
CAAACTGTGACTCTTCTTCCTGCTGCAGATTTGGATGATTT
CTCCAAACAATTG CAACAATCCATG AG CAGTGCTGACTCAACTCAG G CCTAAACTCATGCAGACCACACAAGG
CAGATGG
GCTATATAAACGTTTTCGCTTTTCCGTTTACG ATATATAGTCTACTCTTG TG CAG AATG AATTCTC G
TAACTACATAG CA
CAAGTAGATGTAGTTAACTTTAATCTCACATAG CAATCTTTAATCAGTGTGTAACATTAG GGAG GACTTG AAAG
AG CCAC
CACATTTTCACCGAGG CCACG CGGAGTACGATCGAGTGTACAGTG AACAATGCTAGGG AG AG CTG
CCTATATG GAAGAG C
CCTAATG TGTAAAATTAATTTTAG TAG TG CTAACCC CATGTG ATTTTAATAG CTTCTTA
SEQ ID NO: 21 >QQX12069.1 surface glycoprotein, from genonne accession MW520923 M F V F LVL L P LVSSQCVN FTN RTQLPSAYTNS FTRGVYYP D KV FRSSV LHSTQDLF LP F FS
NVTW F HAI HVSGTNGTKRFD NI PVL P
F N DGVYFASTEKSN II
RGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCNYPFLGVYYHKNNKSWMESEFRVYSSANNCTF EY

VSQPFLMDLEGKQG NFKNLSEFVF KNIDGYFKIYSKHTP IN LVRDLPQGFSALEPLVDLPIGI N
ITRFQTLLALHRSYLTPGDSSSG
WTAGAAAYYVGYLQPRTF L LKYN E NGTITDAVDCAL D PLSETKCILKSFTVE KG IYQTSN FRVQPT
ESIVR FP N ITN LCPF G EVFN
ATRFASVYAW N RKRISNCVADYSVLYNSASFSTFKCYGVSPTKL N DLCFTNVYADSFVIRG
DEVRQIAPGQTGTIADYNYKL PDD
FTG CVIAW NS N N LDSKVGG NYNYLYRLFRKSN LKP FE R DISTE IYQAGSTPC NGVKG F NCYF
PLQSYG FQPTYGVGYQPYRVVVL
SF E LLHAPATVCG PKKSTN LVKN KCVN F N F NG LTGTGVLTESN KKFLPFQQFG
RDIADTTDAVRDPQTLEILDITPCSFGGVSVIT
PGTNTSNQVAVLYQGVNCTEVPVAI HADQLTPTWRVYSTGSNVFQTRAGC LIG AEYVNNSYECDI PIGAG
ICASYQTQTNSPRR

DSTECSN LLLQYGSFCTQLN RALTG IA
VEQDKNTQEVFAQVKQIYKTP PI KDFGG F N FSQI LP DPSKPSKRSFIEDLLF N KVT LADAGF I
KQYG DCLG DIAAR D LI CAQK F NG L
TVLPPL LT DE M IAQYTSALLAGTITSGWTFGAGAALQI P FAM QMAYRF NG IGVTQNVLYE
NQKLIANQF NSAIG KIQDSLSSTAS
ALG K LQDVVNQNAQALNTLVKQLSSN FGAISSVLN DI LSRLDKVEAEVQI DRLITG RLQS LQTYVTQQL
I RAAEIRASAN LAAI KM
SECVLGQSKRVDFCG KGYHLMSFPQSAPHGVVF LHVTYVPAQEKN FTTAPAI CH DG KAH FP REG
VFVSNGTHWFVTQRN FYE
PQI ITTDNTFVSG NCDVVI GIVN NTVYDPLOPE LDSFKEE LDKYFKNHTSPDVDLGDISGINASFVN
IQKEI DR LNEVAKN LN ESLID
LQELG KYEQYI KWPWYIWLGFIAG LIAIVMVTI M
LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
SEQ ID NO: 22 > Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/human/England/MIG457/2020, EVAg Ref-S KU :004V-04032, complete gen onne . UK B 1.1.7 lineage ATTAAAGGTTTATACCTTCCCAGGTAACAAACCAACCAACTTTCGATCTCTTGTAGATCTGTTCTCTAAACGAACTTTA
AAAT
CTGTGTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGAC
AC
GAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGT
CCG
GGTGTGACCGAAAGGTAAGATGGAGAGCCTTGTCCCTGGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTT
TT
ACAG GTTCG CG ACGTG CTCGTACGTG GCTTTG GAG ACTCCGTG G AGGAG GTCTTATCAGAG GCACG
TCAACATCTTAAAG
ATGGCACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTC
GG
ATG CTCG AACTG CACCTCATG G TCATGTTATG GTTGAGCTGGTAG CAG AACTCGAAG G
CATTCAGTACG GTCGTAGTG GT
GAG ACACTTG GTGTCCTTGTCCCTCATGTG G GCG AAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAG
AACGGTAAT
AAAG GAG CTG GTG G CCATAGTTACG G CGCCGATCTAAAG TCATTTG ACTTAG G CGACG AG CTTG
G CACTGATCCTTATGA
AGATTTTCAAG AAAACTG GAACACTAAACATAG CAGTG GTG TTACCCGTG AACTCATG CGTGAG
CTTAACG GAG G G G CAT
ACACTCG
CTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGG
TAAAGCTTCATG CACTTTGTCTG AACAACTGG ACTTTATTG ACACTAAGAG G G GTGTATACTG CTG CCG
TGAACATG AG CA
TGAAATTGCTTGGTACACGGAACGTTCTGAAAAGAGCTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAA
TT
TGACACCTTCAATGGG
GAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAG
AAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCC
TTT
CAACTCTCATGAAGTGTGATCATTGTG GTGAAACTTCATG GCAGACG G G CG ATTTTGTTAAAG CCACTTG
CGAATTTTGTG
GCACTGAGAATTTGACTAAAGAAGGTGCCACTACTTGTGGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCC
AGC
ATGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTGGCTTGAAAACCATTCTTCGT
AA
GGGTG GTCGCACTATTGCCTTTGGAGGCTGTGTGTTCTCTTATGTTGGTTG
CCATAACAAGTGTGCCTATTGGGTTCCACGT
G CTAGCG CTAACATAG GTTGTAACCATACAG GTGTTGTTG GAG AAG GTTCCGAAG
GTCTTAATGACAACCTTCTTG AAATA
CTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTT
TTT
CTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGG
TA
ATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTGGAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTA
TG
CATTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGT
TTTA
CAGAAGGCCGCTATAACAATACTAGATGGAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTG
ATT
TGGCTACTAACAATCTAGTTGTAATGGCCTACATTACAG
GTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTT
TGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGA
GA
CGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTTGTGAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAA
AT
TAAG GAGAGTGTTCAG ACATTCTTTAAG CTTGTAAATAAATTTTTG G CTTTGTGTG
CTGACTCTATCATTATTG GTG GAG CT
AAACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAG
AA
GAAACTG G CCTACTCATG CCTCTAAAAG CCCCAAAAG AAATTATCTTCTTAG AG G GAG
AAACACTTCCCACAGAAGTGTTA
ACAG AG GAAGTTGTCTTGAAAACTG G TGATTTACAACCATTAGAACAACCTACTAGTG AAG CTGTTG AAG
CTCCATTG GTT
G GTACACCAGTTTGTATTAACG G G CTTATGTTG CTCGAAATCAAAGACACAG AAAAGTACTGTG CCCTTG
CACCTAATATG
ATGGTAACAAACAATACCTTCACACTCAAAGGCG GTGCACCAACAAAGGTTACTTTTGGTGATG
ACACTGTGATAGAAGTG
CAAGGTTACAAGAGTGTGAATATCACTTTTGAACTTGATGAAAGGATTGATAAAGTACTTAATGAGAAGTGCTCTG
CCTAT
ACAGTTGAACTCGGTACAGAAGTAAATGAGTTCGCCTGTGTTGTGGCAGATGCTGTCATAAAAACTTTGCAACCAGTAT
CT
GAATTACTTACACCACTG G G CATTGATTTAGATGAGTGG AGTATG G CTACATACTACTTATTTG ATG
AGTCTG GTGAGTTTA
AATTGGCTTCACATATGTATTGTTCTTTTTACCCTCCAGATGAGGATGAAGAAGAAG
GTGATTGTGAAGAAGAAGAGTTTG

AG C CATCAACTCAATATG A GTAT G G TACTG A AG ATG ATTACCAAG GTAAACCTTTG GAATTTG
GTG CCACTTCTG CTG CTCT
TCAACCTG AAGAAG AG CAAGAAG AAGATTG G TTAG AT G ATG ATAGTCAACAAACTGTTGG
TCAACAAG AC G G CAG TG AG
G AC AATCAG ACAACTATTATTCAAACAATT G TT GAG G TTCAA C CT CAATTAG AG AT G
GAACTTACA C CA G TTG TTCAG ACTA
TT G AAG T G AATAG TTTTAG TG G TTATTTAAAACTTA CTG A CAATG TATAC ATTAAAAATG CAG
AC ATTG TG G AAG AA G CTA
AAAAG GTAAAACCAACAGTG GTTGTTAATGCAG CCAATGTTTACCTTAAACATG G AG GAG GTGTTG CAG
G AG CCTTAAAT
AAG G CTACTAACAATG CCATG CAAGTTGAATCTGATGATTACATAG CTACTAATG G AC CACTTAAAG TG
G GTG G TAG TTG T
GTTTTAAG CG GACACAATCTTG CTAAACACTGTCTTCATGTTGTCGG CCCAAATGTTAACAAAG
GTGAAGACATTCAACTTC
TTAA G AG TG CTTATG AAAATTTTAATC AG CAC G AAG TTCTACTTG CA C CATTATTAT CAG CTG
GTATTTTTG GTG CTG A C C CT
ATA CATTCTTTA AG AG TTTG TG TA G ATA CTGTTC G CACAAATGTCTACTTAG CT G TCTTTG
ATAAAAATCTCTAT G A CAAACT
TGTTTCAAG CTTTTTG GAAAT G AAG A G TG AAAAG CAAGTTG AACAAAAGATCG CTG AG ATTC
CTAAAG AG GAAGTTAAG C
CATTTATAACTG AAAGTAAACCTTCAGTTG AACAG A G AAAAC AAG AT G ATAAG AAAATCAAA G CTT
G TG TTG AA G AAG TT
ACAACAACTCTG G AAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTG ACATTAATG G CAAT
CTTC ATC CA G ATT
CTG CCACTCTTGTTAGTG AC ATTG ACATCACTTTCTTAAAGAAAG ATG CT CCATATATAGTG G GTG
ATGTTGTT CAAG AG G G
TGTTTTAACTG CTGTGGTTATACCTACTAAAAAG G CTG GTG G CACTACTG AAATG CTAGCGAAAG CTTT
G AG AAAA G TG CC
AACAGACAATTATATAACCACTTACCCG G GTC AG G GTTTAAATG GTTA CACTG TAG AG GAG G
CAAAGACAGTG CTTAAAA
AG T G TAAAAG T G CCTTTTA CATTCTAC CATCTATTAT CTCTAATG AG AAG CAA G AAATT CTTG
GAACTGTTTCTTG GAATTTG
CG AG AAAT G CTTG CAC ATG C AG AAG AAACACG CAAATTAATG CCT G T CT G TG TG
GAAACTAAAG CCATAGTTTCAACTATA
CAG CGTAAATATAAG G GTATTAAAATACAAG AG G GTGTG GTTGATTATG GTG CTAG
ATTTTACTTTTAC AC CAG TAAAA C A
ACT G TAG CGTCACTTATCAACACACTTAAC GATCTAAATGAAACTCTTGTTACAATG CCACTTG G
CTATGTAACACATG G CT
TAAATTTG GAAG AAG CTG CT C G G TATAT G AG ATCTCT CAAAGTG CC AG CTAC AGTTTCT G
TTTCTT CAC CT G ATG CTGTTAC
AG C G TATAATG G TTATCTTACTTCTT CTT CTAAAA CAC CT G AAG AACATTTTATTG AAACC
ATCT CACTT G CT G G TTC CTATA
AAG ATTG GTCCTATTCTG G ACAATCTACACAACTAG G TATAG AATTTCTTAA G AG AG GTG
ATAAAAG TGTATATTACACTA
G TAATCCTAC CA CATTC CAC CTAG ATG GTG AAGTTATCACCTTTGACAATCTTAAG ACACTT CTTT
CTTTGAG AGAAGTG AG
GACTATTAAG G TG TTTACAA CA GTA GACAACATTAATCTCCACAC G CAAGTTGTG G A CATG TCAAT
G ACATATG GACAACA
GTTTG G TC CA ACTTATTT G GATG GAG CTG ATGTTACTAAAATAAAACCT CATAATTCAC ATG AA G
G TAAAACATTTT ATG TT
TTAC CTAATG AT G ACA CTCTA CG T G TTG AG G CTTTT G AG TACTA C CACAC AACTG ATCC
TAG TTTTC TG G G TAG GTACATGT
CAG CATTAAATCACACTAAAAAGTG G AAATAC C CA CAAG TTAATG GTTTAACTTCTATTAAATG GG
CAG ATAACAACT G TT
ATCTTG CCACTG CATT G TTAA CACT C CAAC AAATA G AG TTG AAG TTTAATC C AC CTG
CTCTACAAG ATG CTTATTACAG AG C
AAG G G CTG GTGAAG CTG ATAACTTTTGTG CA CTTAT CTTAG CCTACTG TAATAAG AC AG TAG
GTG AG TTAG GTG ATGTTAG
AG AAA CAATG AG TTACTTG TTTCAAC ATG CCAATTTAGATTCTTG CAAAAGAGTCTTGAACGTG
GTGTGTAAAACTTGTG G
ACAACAG CA G ACAAC C CTTAAG G G TG TAG AAG CTGTTATGTACATG G G CACACTTTCTTATG
AACAATTTAAG AAA G GTGT
TC AG ATAC CTTG TAC G T G TG GTAAACAAG CT ACAAAATATCTA G TACAACAG G AG TCAC
CTTTTG TTATG ATG TCAG C AC CA
C CT G CT CAG TATG AA CTTAA G CAT G GTACATTTACTTGTG CTAG TG AG TACACTG G
TAATTAC CA G TG T G GT CACTATAAAC
ATATAACTTCTAAAGAAACTTTGTATTG CATAG AC G GTG CTTTACTTACAAAGTCCTCAGAATACAAAG
GTCCTATTACG GA
TGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTG GATG G TG TTG TTT G
TA CAG AAATT
G AC C CTAAG TTG G ACAATTATTATAAG AAAG ACAATT CTTATTTTACAG A G CAA C C AATTG
ATCTT G TAC CAAA C CAAC CAT
ATCCAAACG CAAG CTTCGATAATTTTAAGTTTG TATGTGATAATATCAAATTTG CTG
ATGATTTAAACCAGTTAACTG GTTA
TAAGAAACCTGCTTCAAG AG AG CTTAAAGTTACATTTTTCCCTGACTTAAATG G TG AT G TG GTG G
CTATTGATTATAAACAC
TAC ACAC C CTCTTTTAAG AAA G GAG CTAAATTGTTACATAAACCTATTGTTTG G CATGTTAACAATG
CAACTAATAAAG C CA
CGTATAAACCAAATACCTG GT G TATAC G TTGTCTTTGG AG CAC AAAAC C AG TT G AAAC
ATCAAATTC G TTTG ATG TACTG AA
G T CAG AG G AC G CG CA G G G AATG G ATAATCTTG C CT G C G AAG ATCTAAAAC C A
GTCT CTG AAG AAG TAG TG G AAAATCCTA
CCATACAG AAAGACGTTCTTG AG TG TAATGTG AAAACTACCG AAG TT GTAG G AG
ACATTATACTTAAACC AG CAAATAATA
G TTTAAA AATTA CAG AAG AG GTTG G C CAC ACA G AT CTAATG G CTG
CTTATGTAGACAATTCTAGTCTTACTATTAAGAAAC
CTAATG AATTAT CTAG AG TATTAG G TTT G AAAAC C CTTG TTACTC AT G GTTTAG CTG
CTGTTAATAGTGTCCCTTG G GATAC
TATA G CTAATTATG CTAAG CCTTTTCTTAACAAAGTTG TTAG TACAACTACTAACATA G TTA CA C G
G TG TTTAAA C C GT G TTT
GTACTAATTATATG CCTTATTTCTTTACTTTATTG CTAC AATTG TG TA CTTTTACTAG AAG
TACAAATTCTAG AATTAAA G CAT
CTATG CCGACTACTATAG CAAAGAATACTG TTAAG AG TGTCG G TAAATTTTGTCTAG AG
GCTTCATTTAATTATTTG AAG TC
AC CTAATTTTT CTAAA CTG ATAAATATTA CAATTTG GTTTTTACTATTAAGTGTTTG CCTAG
GTTCTTTAATCTACTCAACCG C
TG CTTTAG GT GTTTTAATGTCTAATTTAG G CATG C CTTCTTACTG TACT G GTTACAG AG AAG G
CTATTTG AACTCTACTAATG
TCACTATTG CAAC CTACT G TA CTG GTT CTATAC CTT G TAG TGTTTG TCTTAGTG
GTTTAGATTCTTTAG ACACCTATCCTTCTT
TAG AAA CTATA CA AATTAC CATTT CATCTTTTAAATG G GATTTAACTGCTTTTG G CTTAGTTG CAG
AG TG GTTTTTG GCATAT
ATTCTTTTCACTAG G TTTTTCTATG TA CTTG GATTG G CT G CAATCATG CAATTG TTTTTC AG
CTATTTTG CAGTACATTTTATT
AG TAATT CTTG G CTTATGTG GTTAATAATTAATCTTGTACAAATG GCCCCGATTTCAG CTATG
GTTAGAATGTACATCTTCTT
TG CATCATTTTATTAT G TAT G G AAAAG TTATG TG CATG TT G TAG AC G G TTG TAATT CAT
CAACTTG TATG ATG T G TTAC AAA
C G TAATAG AG CAACAAG AG TCG AATGTACAACTATTGTTAATG GTGTTAGAAG
GTCCTTTTATGTCTATG CTAATG GAG GT

AAAG G CTTTTG CAAACTAC AC AATTG GAATTGTG TTAATTGTGATACATTCTGTG CTG G TA G
TACATTTATTAG TG AT G AAG
TTG CG AG AG ACTTGTCA CTACAG TTTAAAAG ACCAATAAATCCTACTG
ACCAGTCTTCTTACATCGTTGATAGTGTTACAGT
GAAGAATG GTTCCATCCATCTTTACTTTGATAAAG CTG GTCAAAAG ACTTATG AAAG AC ATTCT CTCT
CTCATTTTGTTAACT
TAG ACAACCTG AG AG CTAATAAC ACTAAA G G TT CATT G CCTATTAATG TTATAG TTTTT G AT
G GTAAATCAAAATGTGAAG
AATCATCTG CAAAATCAG CGTCTGTTTACTACAGTCAG C TTAT G TG TCAAC CTATA CTG TTACT AG
AT CAG G CATT AG TG TC
TG ATG TT G GTGATAGTG CG G AAG TT G CAG TTAAAATG TTTG AT G
CTTACGTTAATACGTTTTCATCAACTTTTAACGTACCA
ATG GAAAAACTCAAAACACTAGTTG CAACTG C AG AAG CTG AACTTG CAAA G AATG TG T CCTTAG
A CAATGT CTTAT CTACT
TTTATTTCAG CAGCTCG G CAAG GGTTTGTTG ATTCAGATGTAG
AAACTAAAGATGTTGTTGAATGTCTTAAATTGTCACATC
AATCTGACATAG AAGTTACTG G CG ATAGTTGTAATAACTATATG CT CACCT ATAAC AAAG TTG
AAAACATG ACACC CC GTG
ACCTTG GTG CTTGTATTGACTGTAGTG CG CGTCATATTAATG CG CAGG TAG
CAAAAAGTCACAACATTGCTTTG ATATG GA
AC G TTAAAG ATTT CAT G TCATTG T CTG AAC AACTAC G AAAACAAATAC G TAG TG CTG
CTAAAAAGAATAACTTAC CTTTTAA
G TTG AC ATG T G CAACTACTAG ACAAG TT G TTAATGTTGTAACAAC AAAG ATAG CA CTTAA G G
GTG GTAAAATTGTTAATAA
TTG GTTG AAG CAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTG CTG CTATTTTCTATTTAATAA CAC
CTG TT CATGTC AT
GTCTAAACATACTGACTTTTCAAGTGAAATCATAG GATACAAG G CTATTGATGGTG GTGTCACTCGTG
ACATAG CATCTAC
AG ATACTTG TTTTG CTAACAAACATG CTG ATTTTG A CACAT G GTTTAG CCAGCGTG GTGG TAG
TTATACTAAT G ACAAAG CT
TG CCCATTGATTG CTG CAGTCATAAC AAG AG AAGTG G GTTTTG TCGTG CCTG GTTTG CCTG G
CACGATATTACG CACAACT
AATG GTG ACTTTTTG CATTTCTTACCTAG AG TTTTTAG T G CAGTTG G TAACATCTG TTAC A
CACCAT CAAAACTTATAG AG TA
CACTGACTTTG CAACATCAG CTTGTGTTTTG G CTG CTG AATGTACAATTTTTAAAGATG CTTCTG
GTAAGCCAGTACCATAT
TGTTATGATACCAATGTACTAGAAG GTTCTGTTG CTTATGAAAGTTTACG CCCT G ACA CAC G TTATG T
G CT CATG GATG G CT
CTATTATTCAATTTCCTAACACCTACCTTG AAG GTTCTGTTAG AG TG GTAACAACTTTTGATTCTG AG
TACTG TAG G CAC G G
CACTTGTGAAAG ATCAGAAG CTG G TG TTTG T G TAT CTACTAG TG G TAG ATGG G TA CTTAA C
AAT G ATTATTACAGATCTTTA
CCAG G AG TTTTCTG TG G TG TA G ATG CTG
TAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTG GTG CTTTG GA
CATATCAG CATCTATAGTAG CTG GTGGTATTGTAG CTATCGTAGTAACATG CCTTG C CTACTATTTTATG
AG GTTTAG AAG A
G CTTTTGGTG AAT ACAGTCATG TAG TTG CCTTTAATACTTTACTATTCCTTATGTCATT CACTG TACT
CTG TTTAA CACCA GTT
TACTCATTCTTACCTG G TG TTTATTCT G TTATTTACTT G TACTTG A CATTTTATCTTACTAATG
ATGTTTCTTTTTTAG CACATA
TT CAG T G G AT G G TTAT G TTCA CACCTTTAG TACCTTTCTG G ATAACAATTG
CTTATATCATTTGTATTTCCACAAAG CATTTCT
ATTG G TT CTTTAG TAATTACCTAAAG A G ACG TG TAGTCTTTAATG GTGTTTCCTTTAGTACTTTTG
AAGAAG CTG CG CT G TG
CAC CTTTTTG TTAAATAAAG AAATGTATCTAAAGTTG C G TA G TG ATGTG CTATTACCTCTTACG
CAATATAATAG ATACTTA
G CTCTTTATAATAAGTACAAGTATTTTAGTGG AG CAATG G ATACAACTAG CTAC AG AG AAG CTG
CTTGTTGTCATCTCG CA
AAG G CTCTCAAT G ACTT CA G TAACTC AG GTTCTG ATG TTCTTTACCAA CC ACC ACAAAC
CTCTAT CACCT CAG CTGTTTTG CA
G AG TG GTTTTAGAAAAATG G CATTCCCATCTG GTAAAG TT G AG G GTTGTATG GTACAAG
TAACTTGTG GTACAACTACACT
TAACGGTCTTTG G CTTGATGACGTAGTTTACTGTCCAAG ACATGTG ATCTG CACCTCTG AAGACATG
CTTAACCCTAATTAT
G AA G ATTTACTC ATTCG TAAG TCTAAT CATAATTTCTTG GTACAG GCTGGTAATGTTCAACTCAG G
GTTATTGG ACATTCTA
TG CAAAATTGTGTACTTAAG CTTAAG GTTGATACAG CCAATCCTAAGACACCTAAGTATAAGTTTGTTCG
CATTCAACCAG G
ACAGACTTTTTCAGTGTTAG CTTGTTACAATG G TTCACCATCTG GTGTTTACCAATGTG CTATG AG
GCCCAATTTCACTATTA
AG G G TT CATT CCTTAATG GTTCATGTG G TAG TG TT G GTTTTAACATAGATTATG
ACTGTGTCTCTTTTTGTTACATG C AC C AT
ATG GAATTACCAACTG G AG TTCATG CTG G CACAGACTTAGAAG GTAACTTTTATG G ACCTTTTGTT G
AC AG GCAAACAG CA
CAAG CAG CTG G TACG GACACAACTATTACAGTTAATGTTTTAG CTTGGTTGTACG CTG CTGTTATAAATG
GAG ACAG GTG G
TTTCTCAATCG ATTTACCACAACTCTTAATGACTTTAACCTTGTG G CTATGAAGTACAATTATG AACCT CTAA
CA CAA G ACCA
TG TTG A C ATA CTAG G ACCTCTTTCTG CTCAAACTG G AATTG CCGTTTTAG ATATGTGTG
CTTCATTAAAAGAATTACTG CAA
AATG GTATGAATG G ACGTACCATATTG G GTAG TG CTTTATTAG
AAGATGAATTTACACCTTTTGATGTTGTTAGACAATG CT
CAG GTGTTACTTTCCAAAGTG CAGTGAAAAG AACAATCAAG G G TACAC AC CACTG G TT G TTACTC
AC AATTTT G ACTT CA CT
TTTAG TTTTAGTCCAG AG TACTC AATG GTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTG
CTATG G GTATTAT
TG CTATG TCTG CTTTTG CAATGATGTTTGTCAAACATAAG CATG
CATTTCTCTGTTTGTTTTTGTTACCTTCTCTTG CC ACTG T
AG CTTATTTTAATAT G GTCTATATG CCTG CTAGTTG G GTGATGCGTATTATGACATG GTTG GATATG
GTTGATACTAGTTTG
AAG CTAAAAGACTGTGTTATGTATG CAT CAG CTG TAG T G TTACTAATC CTTATG ACA G CAAG
AACTG TG TAT G AT G ATG GT
G CTAGG AG AG TGTG G ACA CTTAT G AAT G TCTTG AC ACTC G TTT ATAAAG TTTATTATG
GTAATG CTTTAGATCAAG CC ATTT
CCATGTG GG CTCTTATAATCTCTGTTACTTCTAACTACTCAG GTG TAG TTACAA CTGT CATG TTTTTG G
CCAG AG GTATTGTT
TTTATG TG T GTTG AG TATTG CCCTATTTTCTTCATAACTG GTAATACACTTCAGTGTATAATG
CTAGTTTATTG TTTCTTAG GC
TATTTTTGTACTTGTTACTTTG G CCTCTTTTGTTTACTCAACCG CTACTTTAG ACTG ACTCTTG
GTGTTTATGATTACTTAGTTT
CTACACAG GAGTTTAG ATATATGAATTCACAGG G ACTA CTCC CACCCAAG AA TAG CATAGATG
CCTTCAAACTCAACATTA
AATTGTTG G GTGTTG GTG G CAAACCTTG TAT CAAAGTAG CCACTGTAC AG TCTAAAATGTCAG ATG
TAAAG TG CAC ATCA R
TAG TCTTACTCT CAG TTTTG CAACAACTCAGAGTAG AATCATCATCTAAATTGTG G G CT
CAATGTGTCCAG TTACACAATG A
CATTCTCTTAG CTAAAG ATACTACTG AAG C CTTTGAAAAAATG GTTTCACTACTTTCTGTTTTG
CTTTCCATG CAG G GTG CTG
TAG ACATAAACAAG CTTTGTG AAGAAATG CT G G AC AAC AG G G CAA CCTTA CAAG CTATAG
CCTCA G AG TTTAG TTCCCTTC

CAT C ATAT G CAG CTTTTG CTACTG CTCAAGAAG CTTAT G AG C AG G CTGTTG CTAATG GTG
ATTCTGAAGTTGTTCTTAAAAA
GTTGAAG AAGTCTTTGAATGTG G CTAAATCTG AATTTGACCGTG ATG C AG CC ATG CAA CGTAAGTT
G GAAAAGATG G CT G
ATCAAG CTATG ACCCAAATGTATAAACAG G CTAG AT CTG A G GACAAG AG G G
CAAAAGTTACTAGTG CTATGCAG ACAATG
CTTTTCACTATG CTTAGAAAG TTG GATAATGATG CACTCAACAACATTATCAACAATG CAAG A G ATG
GTTGTGTTCCCTTG A
ACATAATACCTCTTACAACAG C AG CCAAACTAATG GTTGTCATACCAG A CTATAACA CATATAAAAATAC
GTGTG ATG GTA
CAACATTTACTTATG C AT CAG CATTGTG G G AAATCCAACAG GTTG TAG ATG CAG ATAG
TAAAATTGTTCAACTTAGTG AAA
TTAG TAT G G A CAATT CACCTAATTTAG CATGG CCTCTTATTGTAACAG CTTTAAG G G CCAATTCTG
CT GTCAAATTA CAG AA
TAATG AG CTTAGTCCTGTTG CACTACG ACAGATGTCTTG TG CTG CCG GTACTACACAAACTGCTTG
CACTGATGACAATG C
GTTAGCTTACTACAACACAACAAAG G GAG G TAG GTTTGTACTTG CACTGTTATCCG ATTTACAG G
ATTTGAAATG G G CTAG
ATTCCCTAAG AG TG AT GG AACTG GTACTATCTATACAGAACTG G AACCACCTTG TAG G TTTG TTAC
AG AC ACACCTAAAG G
TCCTAAAGTG AA GTATTTATACTTTATTAAAG GATTAAACAACCTAAATAG AG G TATG GTACTTG
GTAGTTTAG CTG CCACA
GTACGTCTAC AA G CTG GTAATG CAAC AG AAG T G CCTG CCAATTCAACTG TATTATCTTTCTGTG
CTTTTG CT GTAG ATG CTG
CTAAAG CTTACAAAGATTATCTAG CTAGTG
GGGGACAACCAATCACTAATTGTGTTAAGATGTTGTGTACACACACTG GTA
CTG GTC AG G CAATAACAGTTACACCG G AA G CC AATATG GATCAAGAATCCTTTG GTG GT G CAT
CGT GTTG TCTG TACT G CC
GTTG CCACATAGATCATCCAAATCCTAAAG GATTTTGTG ACTTAAAAG GTAAGTATGTA CAAATACCTA CAA
CTTGTG CTAA
TG ACCCTGTG GGTTTTACACTTAAAAACACAGTCTGTACCGTCTG CG G TATGTG G AAAG GTTATG
GCTGTAGTTGTGATCA
ACTCCG C GAACCCATG CTTCAGTCAGCTG ATGCACAATCGTTTTTAAACG G GTTTG CG GTGTAAGTG
CAG CCCGTCTTACA
CCGTGCG G CAC AG G CACTAG TACTG ATGTCGTATACAG G G CTTTTGACATCTACAATG ATAAAGTAG
CTG GTTTTG CTAAA
TT CCTAAAAACTAATTG TTGT CG CTTCCAAGAAAAG G AC G AAG ATG AC AATTTAATT G ATT
CTTA CTTT GTAGTTAAG AG AC
ACACTTTCTCTAACTACCAACATGAAG AAACAATTTATAATTTACTTAAG G ATTGTCCAG CTGTTG CTAAA
CATG A CTTCTTT
AAGTTTAGAATAGACG G TG A CATG GTACCACATATATCACGTCAACGTCTTACTAAATACACAATG G CAG
AC CTCG TCTAT
G CTTTAAG G CATTTTG ATGAAG GTAATTGTG A CACATTAAAAG
AAATACTTGTCACATACAATTGTTGTGATG ATGATTATT
TCAATAAAAAGGACTG G TATG ATTTTGTAGAAAACCCAGATATATTACG CG TATAC GC CAA CTTAG
GTGAACG TGTACG CC
AAG CTTTGTTAAAAACAGTACAATTCTGTG ATG CCATG CGAAATG CT G GTATTGTTG G TGTA CTG A
CATTA G ATAATCAAG
ATCTCAATG G TAACTG GTATGATTTCG GTG ATTTCATACAAACCACG CCAG GTAGTG G AGTTCCTGTTG
TAG ATTCTTATTA
TT CATTGTTAAT G CC TATATTAACCTTG A CCAG G G CTTTAACTG CA G AGTCACATGTTG
ACACTGACTTAACAAAGCCTTAC
ATTAAGTGG G ATTTGTTAAAATATG ACTTCACG GAAGAGAG GTTAAAACTCTTTG ACC
GTTATTTTAAATATTGG G AT CAG
ACATACCACCCAAATTGTGTTAACTGTTTG GATG ACAG ATGCATTCTG CATTGTG
CAAACTTTAATGTTTTATTCTCTACAGT
GTTC CC A CTTA CAAGTTTTG G ACC ACTAG TGA G AAAAATATTTGTT G ATG G TG TTCC ATTT
G TAG TTTCAACTG GATACCAC
TT CAG AG AG CTAG GTGTTGTACATAATCAG G ATGTAAACTTACATAG CT CTAG ACTTAGTTTTAAG
GAATTACTTGTGTATG
CTG CTG ACCCTG CTATG CA CG CT G CTTCTG GTAATCTATTACTAG ATAAACG CACTACGTG
CTTTTCAGTAG CTG CACTTACT
AACAATGTTG CTTTT CAAACT GTCAAACCT G GT AATTTTAACAAAGACTT CTATG ACTTTG CTG
TGTCTAAG G GTTTCTTTAA
G GAAG GAAGTTCTGTTG AATTAAAACACTTCTTCTTTG CT CAG G ATGGTAATG CTG CTAT C AG CG
ATTATGACTACTATCGT
TATAATCTACCAACAAT GTG TG ATATC AG
ACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACTTTGATTGTTACG ATG
GTG G CTGTATTAATG CTAACCAAGTCATCGTCAACAACCTAGACAAATCAG CTG GTTTTCCATTTAATAAATG
G G GTAAG G
CTAGACTTTATTATG ATTCAATG AGTTATG AG G ATC AAG AT G CACTTTTCG CATATACAAAACG
TAATG TC AT CCCTACTAT
AACTCAAATGAATCTTAAGTATG CCATTAGTG CAAAG AATAG AG CTCG CACC GTAG CTG
GTGTCTCTATCTG TAGTAC TAT
G AC CAATAG ACAG TTT CAT CAAAAATTATTG AAATCAATAG CCGC CACTAG AG GAG
CTACTGTAGTAATTG GAACAAG CAA
ATTCTATG GTG GTTG G CAC AAC ATG TTAAAAACTGTTTATAGTG ATGTAGAAAACCCTCATCTTATG G
GTTG G G ATTATCCT
AAATGTG ATAG AG CCATG CCTAACATG CTTAG AATTATG G CCT C ACTT GTT CTTG CTCG
CAAACATACAACGTGTTGTAG CT
TGTCACACCGTTTCTATAGATTAG CTAATG AGTGTG CT CAAG TATTG AGTG AAATG GTCATGTGTG G
CG GTTCACTATATGT
TAAACCAG GTG GAACCTCATCAG GAG AT G CCACAACTG CTTATG
CTAATAGTGTTTTTAACATTTGTCAAGCTGTCACG G C
CAATGTTAATG CACTTTTATCTACTGATG GTAACAAAATTG CCGATAAGTATGTCCG CAATTTACAACACAG
ACTTTAT G AG
TG TCTCTATAG AAATAG AG ATGTTG A CACAG ACTTTGTGAATG AGTTTTACG CATATTTG
CGTAAACATTTCTCAATG ATG A
TACTCTCTG AC G ATG CTGTTGTGTGTTTCAATAGCACTTATG CAT CTCAA G GT CTAG TG G CTAG
CATAAAGAACTTTAAGTC
AGTTCTTTATTATCAAAACAATGTTTTTATGTCTG AAG CAAAATGTTG G ACTG AGACTG AC CTTA
CTAAAG G AC CTCATG AA
TTTTG CT CT C AACATA CAATG CTAGTTAAACAG GGTGATG ATTATGTG TACCTTCCTTACCC AG
ATCC AT CAA G AATCCTAG
G G G CC G G CTGTTTTGTAGATG ATATCGTAAAAACAGATG GTACACTTATGATTGAACG
GTTCGTGTCTTTAGCTATAGATG
CTTACCCACTTACTAAACATCCTAATCAG GAGTATG CTG ATGTCTTTCATTTGTACTTACAATACATAAGAAAG
CTACATGAT
G AG TTAACAG G AC ACAT GTTAG A CATGTATTCT G TTATG CTTACTAATGATAACACCTCAAG G
TATTG G G AACCTG AGTTTT
ATG AGG CTATG TA CA CACCG CATACAGTCTTACA G G CTGTTG G G G CTTGTGITCITTG
CAATTCACAGACTTCATTAAGATG
TG GTG CTTG CATACGTAG ACCATTCTTATGTTGTAAATG CTGTTACG
ACCATGTCATATCAACATCACATAAATTAGTCTTGT
CTGTTAATCCGTATGTTTG CAATG CT CCA G GTTGTG ATG TCACAG ATG TG A CTCAA CTTTACTTAG
GAG GTATG A G CTATTA
TT GTAAATCACATAAAC CACCC ATTAG TTTTCCATTGTGTG CTAATG G AC AAG TTTTT G
GTTTATATAAAAATACATGTGTTG
GTAG CG ATAATGTTACTG ACTTTAATG CAATTG CAA CATG TG ACTG G ACAAATG CTG
GTGATTACATTTTAG CTAAC A CCTG

TACTG AAAG ACT CAAG CTTTTTG CAG CAGAAACG CTCAAAG CT ACTG AG GAG A
CATTTAAACTGTCTTAT G GTATTG CTAC
TGTACGTGAAGTG CTGTCTGAC AG AG AATTACATCTTTCATG G G AAGTTG
GTAAACCTAGACCACCACTTAACCGAAATTA
TGTCTTTACTG GTTATCGTGTAACTAAAAACAG TAAAGTACAAATAG G AG AG TAC A CCTTTG AAAAAG
GT G ACTATG G TG A
TG CTG TTGTTTA CCG AG GTACAACAACTTACAAATTAAATGTTG G
TGATTATTTTGTGCTGACATCACATACAGTAATG CCA
TTAAGTG CACCTACACTAGTG CCACAAG AG CACTATGTTAGAATTACTG G CTTATAC CCAAC A
CTCAATATCTCAG ATG AG
TTTTCT AG CAATGTTG CAAATTATCAAAAG GTTGGTATG CAAAAGTATTCTACACTCCAG G G AC
CACCTG GTACTG GTAAG
AGTCATTTTG CTATTG G CCTA GCT CTCTA CTA CC CTTCTG CTCG CATAG TGTATACAG CTTG CT
CTCATG CC G CTGTTGATG C
ACTATGT G AG AAG G CATTAAAATATTTG CCTATAGATAAATGTAGTAG AATTATACCTG CAC GTG
CTCGTGTAGAGTGTTT
TG ATAAATTCAAAGTG AATTCAACATTAGAACAG TATGTCTTTTGTACTGTAAATG CATTGCCTG AG ACG
AC AG CAG ATAT
AGTTGTCTTTGATG AAATTTCAATGG CCACAAATTATG ATTTGAGTGTTGTCAATG CCAGATTACGTG CTAAG
CACTATGTG
TACATTG G CGACCCTG CTCAATTAC CT G C ACCAC G CACATTG CTAACTAAG G
GCACACTAGAACCAG AATATTTCAATTCAG
TGTGTAGACTTATG AAAACTATAG G TCCAGACATGTTCCTCG GAACTTGTCG G CGTTGTCCTG CTG
AAATTGTTGACACTGT
G AG TG CTTTG GTTTATGATAATAG G CTTAAAG CACATAAAGACAAATCAG CT CAATG
CTTTAAAATGTTTTATAAG G GTGT
TAT CACG C ATG AT GTTTCATCTG CAATTAAC AG G CCACAAATAG G CGTG GTAAG AG AATTC
CTTACACG TAACC CTG CTTG
GAG AAAAG CTGTCTTTATTTCACCTTATAATTCACAGAATG CTGTAG CCTCAAAGATTTTGG G ACTAC
CAACTCAAACTGTT
GATTCATCACAG G G CT CAG AATATG ACTAT G TCATATT CACT C AAACCA CTG AA ACAG CT
CACT CTTG TAAT GTAAA CAG AT
TTAATGTTG CTATTAC CA GAG CAAAAG TAG G CATACTTTG CATAATGTCTG ATA G A G ACCTTTAT
G ACAAGTT G CAATTTAC
AAGTCTTGAAATTCCACGTAG G AATGTG G CAA CTTTA CAA G CT G AAAATG TAACAG G ACT
CTTTAAA G ATTGTAGTAAG GT
AATCACTG G GTTACATCCTACACAG G CA CCTACAC ACCTC AGTG TTG ACACTAAATTCAAAACTGAAG
GTTTATG TGTT G AC
ATACCTG GCATACCTAAG G ACATGACCTATAG AAG ACT CATCTCTAT G ATG G GTTTTAAAATG
AATTATCAAGTTAATG GTT
ACC CTAA CATGTTTATC ACCCG CG AAG AAG CTATAAG ACATGTACGTG CATG GATTG G CTTC G
ATG TCG AG G GGTGTCATG
CTACTAG AG AAG CTGTTG GTACCAATTTACCTTTACAG CTAG GTTTTTCTACAG GTGTTAACCTAGTTG
CTGTACCTACAG G
TTATGTTG ATA CACCTAATAATACAG ATTTTT CCA G A GTTA GTG CTAAAC CAC CG CCTG G AG
ATCAATTTAAA CACCT CATA
CCACTTATGTACAAAG G ACTT CCTTG GAATGTAGTG CGTATAAAG ATTG TACAAATGTTAAG TG AC
ACACTTAAAAATCTCT
CT G ACAG AGTCGTATTTGTCTTATG G G CAC ATG G CTTTGAGTTGACATCTATG AAGTATTTTGTG
AAAATAG G A CCTG AG C
G CACCTGTTG TCTATGTG ATAG ACGTG C CA CATG CTTTTCCACTG CTTCAG ACACTTATG CCTGTTG
G CATCATTCTATTG GA
TTTGATTACGTCTATAATCCGTTTATGATTG ATGTTCAACAATG G G GTTTTACAG GTAACCTACAAAG C AA
CCAT GATCTGT
ATTGTCAAGTCCATG G TAATG CACATGTAG CTAGTTGTGATG CAATCATGACTAG GTGTCTAG CTG
TCCACG AG TG CTTTG
TTAAG CG TGTT G ACT G GACTATTG AATATCCTATAATTG GTG ATG AACTGAAG ATTAATG CG G
CTTG TAG AAAG GTTCAAC
ACATGGTTGTTAAAG CTG CATTATTAG C AG A CAA ATTCCCAGTTCTT CACG ACATTG
GTAACCCTAAAG CTATTAAG TG T GT
ACCT CAA G CT G ATGTA G G AT G G AA GTTCTATG ATG CACAG CCTTGTAGTGACAAAG
CTTATAAAATAG AAGAATTATTCTA
TT CTTAT G CC ACACATTCTG ACAAATTCAC AG AT G GTGTATG CCTATTTTGGAATTG
CAATGTCGATAGATATCCTG CTAATT
CCATTGTTTGTAGATTTG ACACTAGAGTG CTATCTAACCTTAACTTG CCTG GTTGTGATG GTG G
CAGTTTGTATGTAAATAA
ACATGCATTCCACACACCAG CTTTTGATAAAAGTG
CTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCC
ATG TG AG TCT CAT G G AAAACAAGTAGTGTCAG ATATAG ATTAT GTAC CACTAAAGT CT G
CTACGTGTATAACACGTTG CAA
TTTAG GTG G TG CT GTC TGTAG ACAT CATG CTAATGAGTACAG ATTGTATCTCGATGCTTATAACATG
ATG AT CTCAGCTG G C
TTTAG CTTGTG G G TTTACAAACAATTTGATACTTATAACCTCTG G AACACTTTTA CAAG A CTTCA
GAGTTTAG AAAATG TG G
CTTTTAATGTTGTAAATAAG G GACACTTTG ATG GACAACAG G GTGAAG TACCAGTTTCTAT
CATTAATAACA CTG TTTAC AC
AAAAGTTGATG GTG TTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAG CATTTG AG
CTTTG G G CTAA
G CG CAACATTAAACCAGTACCAG AG G TGAAAATACTCAATAATTTG G GTGTG G ATATTG CTG
CTAATACTGTG ATCTG G GA
CTACAAAAG AG AT G CT CCAG CACATATATCTACTATTG GTGTTTG TTCTATG A CTG A CATAG
CCAAG AAACCAACTGAAAC
GATTTGTG CACCACTCACTGTCTTTTTTG ATG G TAG AGTTG ATG GTCAAGTAG ACTTATTTAGAAATG
CCCGTAATG GTGTT
CTTATTACAGAAG GTAGTGTTAAAG GTTTACAACCATCTGTAG GT CCCAAACAAG CTAGTCTTAATG G
AGTCACATTAATT
G G AG AAG CCGTAAAAACACAG TTCAATTATTATAAGAAAGTTG ATG GTGTTGTCCAACAATTACCTG
AAACTTACTTTACTC
AGA GTAG AAATTTACAA G AATTTAAACCC AG G AG T CAA ATG G
AAATTGATTTCTTAGAATTAGCTATG GATG AATTCATTG
AACG GTATAAATTAG AA G G CTATGCCTTCGAACATATCGTTTATG G AG ATTTTA GTCATAGTC
AGTTAG GTG GTTTACATCT
ACTGATTG GACTAGCTAAACGTTTTAAG GAATCACCTTTTG AATTAGAAGATTTTATTC CTATG
GACAGTACAGTTAAAAAC
TATTTCATAACAGATG CG CAAACAG G TT CATCTAA GTGTGTG TGTTCTG TTATTGATTTATTACTTG
ATG ATTTTGTTG AAAT
AATAAAATCCCAAGATTTATCTGTAGTTTCTAAGGTTGTCAAAGTGACTATTG ACTATACAG AAATTTCATTTATG
CTTTGTG
TAAAGATG G CCATGTAGAAACATTTTACCCAAAATTACAATCTAGTCAAGCGTG G CAACCG G GTGTTG
CTATG CCTAATCT
TTACAAAATG CA AAG AATG CTATTA GAAAAGTGTGACCTICAAAATTATG GTG ATAGTG
CAACATTACCTAAAG G C ATA AT
G AT G AAT GTC G CAAAATATACTCAACTGTGTCAATATTTAAACACATTAACATTAG
CTGTACCCTATAATATG A G AG TTATA
CATTTTG GTG CTG GTTCTGATAAAG GAG TTG CAC CAG GTAC AG CTG TTTTAAG AC AGTG
GTTGCCTACGG GTACG CTG C TT
GTCGATTCAGATCTTAATGACTTTGTCTCTGATG CAGATTCAACTTTGATTG GTG ATTGTG
CAACTGTACATACAG CTAATA
AATG GG ATCTCATTATTAGT G ATATGTA CG ACC CTAAG ACTAAAAATG TTACAAAAG AAAATGA
CTCTAAAGA G G GTTTTT

TCACTTACATTTGTG GGTTTATACAACAAAAG CTAG CTCTTG GAG GTTCCGTG G CTATAAAGATAACAG
AACATTCTTG GA
ATG CTG ATCTTTATAAG CTCATG G GACACTTCG CAT G GTG GACAG CCTTTGTTACTAATGTGAATG
CGTCATCATCTGAAG C
ATTTTTAATTG GATGTAATTATCTTG G CAAACC AC G CG AACAAATAGATGGTTATGTCATG CAT G
CAAATTACATATTTTG G
AG G AATACAAATCCAATTCAGTTGTCTTCCTATTCTTTATTTG ACATG AG TAAATTTCC CCTTAAATTAAG
G G GTACTG CTGT
TAT G TCTTTAAAAG AAG GTCAAATCAATGATATGATTTTATCTCTTCTTAGTAAAG G TAG
ACTTATAATTAG AG AAAACAAC
AG A G TTG TTATTTCTAG T G ATG TTCTTG TTAACAA CTAAA C G AAC AATGTTTG
TTTTTCTTGTTTTATTG CC ACTAG TCTCTAG
TC AG TG TG TTAATCTTAC AACCAG AACTCAATTACCCCCTG CATACACTAATTCTTTCACACGTG
GTGTTTATTACCCTGACA
AAGTTTTCAG ATCCTCAGTTTTACATTCAACTCAG G ACTT G TTCTTAC CTTT CTTTTCCAATG TTACTTG
G TTCCATG CTAT CT
CTG G GACCAATG GTACTAAG AG GTTTGATAACCCTGTCCTACCATTTAATGATG GTGTTTATTTTG
CTTCCACTG AG AAG TC
TAA CATAATAAG AG G CT G G ATTTTTG G T ACTACTTT AG ATT C G AA G ACCCAG TC
CCTACTTATTG TTAATAA C G CTACTAAT
G TTG TTATTAAAG T CTG T G AATTT CAATTTT G TAATG AT CCATTTTTG G
GTGTTTACCACAAAAACAACAAAAGTTG G ATG G
AAAGTG AG TTCAG AG TTTATTCTAGTG CGAATAATTG CACTTTTG AATATGTCTCTCAG
CCTTTTCTTATG GACCTTGAAG G
AAAACAG G GTAATTTCAAAAATCTTAG G GAATTTGTGTTTAAG AATATTG ATG
GTTATTTTAAAATATATTCTAAG CACACG
CCTATTAATTTAGTG CGTGATCTCCCTCAG G GTTTTTCG G CTTTAGAACCATTG GTAG ATTTG CCAATAG
GTATTAACATCAC
TAG GTTTCAAACTTTACTTG CTTTACATAGAAGTTATTTGACTCCTG GTG ATTCTTCTTCAGG TTG G ACAG
CTG GTG CTG CA
G CTTATTATGTG G G TTAT CTTC AA CCTAG G ACTTTTCTATTAAAATATAATG AAAATG G
AACCATTACAG ATG CTG TA G ACT
GTG CACTTG ACCCTCTCTC AG AAAC AAAG T G TAC GTTG AAATC CTTC A CTG TAG AAAAAG G
AATCTATC AAA CTTCTAACTT
TAG AGTCCAACCAACAG AATCTATTGTTAGATTTCCTAATATTACAAACTTGTG CCCTTTTG
GTGAAGTTTTTAACG CC ACCA
GATTTG CATCTGTTTATG CTTG GAACAG G AAG AG AATCAG C AACTG TGTTG CT G ATTATTCTG
TCCTATATAATT CC G CATC
ATTTTCC ACTTTTAAG TG TT ATG G AG TG TCTC CTACTAAATTAAATG ATCTCTG
CTTTACTAATGTCTATG CAG ATTCATTTGT
AATTAG AG GTG ATG AAG TC AG ACAAATC G CTCCAG G GCAAACTG G AAAG ATTG
CTGATTATAATTATAAATTACCAG ATG
ATTTTAC AG G CTG CGTTATAG CTTG G AATTCTAACAATCTTGATTCTAAG G TT G GT G G
TAATTATAATTACCT G TATA G ATT
GTTTAG G AAG TCTAATCTC AAACCTTTTG AG AG AG ATATTTCAACTG AAAT CTAT CAG G CCGG
TAG CACACCTTGTAATGG
TGTTG AAGGTTTTAATTGTTACTTTCCTTTACAATCATATG GTTTCCAACCCACTTATG GTGTTG GTTACCAAC
CATAC AG AG
TAG TAG TACTTTCTTTTG AACTT CTACATG CA CCAG C AACTG TTT G TG G
ACCTAAAAAGTCTACTAATTTG GTTAAAAACAA
ATGTGTCAATTTCAACTTCAATG G TTTAACAG G CAC AG GTGTTCTTACTG AG TCTAACAAAAAG TTTCT
G CCTTTCC AA CAA
TTTGG C AG AG ACATTGATG ACACTACTG ATG CT G TC C G TG ATCCA CAG A C ACTTG AG
ATTCTT G A CATTA CACCAT GTT CTT
TT G GTG GTGTCAGTGTTATAACACCAG GAACAAATACTTCTAACCAG G TT G CT G TTCTTTATCAG G
GTGTTAACTG CACAG
AAG TCCCT G TT G CTATTC AT G CAG ATC AA CTTACTCCT ACTTG G C G TG TTTATT CTAC
AG GTTCTAATGTTTTTCAAACACGT
G C AG G CT G TTTAATAG G G G CTG AACATGTCAACAACTCATATG AG TG TG A C ATACCC
ATTG GTG CAG GTATATG CGCTAGT
TAT CAG ACTCAG ACTAATTCTCATCG G CG G G CAC GTAGTG TAG CTAGTCAATCCATCATTG
CCTACACTATGTCACTTG GTG
CAG AAAATTCAGTTG CTTACTCTAATAACTCTATTG CC ATA CCCATAAATTTTACTATTA G TG TTACCAC
AG AAATTCTA CCA
GTGTCTATGACCAAG ACATCAG TAG ATT GTAC AATGTACATTTGTG GTGATTCAACTGAATG CAG
CAATCTTTTGTTG CAAT
ATG G CAGTTTTTGTACACAATTAAACCGTG CTTTAACTG GAATAG
CTGTTGAACAAGACAAAAACACCCAAGAAGTTTTTG
CAC AAG TC AAACAAATTTA CAAAAC ACCAC CAATTAAAG ATTTT G GTG
GTTTTAATTTTTCACAAATATTACCAGATCCATCA
AAACCAAG C AA G AG GTCATTTATTG AAGATCTACTTTTCAACAAAGTG ACACTTG CAG ATG CTG G
CTTCATCAAACAATAT
G GTGATTGCCTTG GTG ATATTG CTG CTAG AG AC CTCATTTG TG CA CAAAAG TTTAACG G
CCTTACTGTTTTG CCACCTTTG C
TCACAGATGAAATGATTG CTCAATACACTTCTG CACTGTTAG CG G GTACAATCACTTCTG GTTG G A
CCTTT G GTG CAG GTG
CTG CATTACAAATACCATTTG CTATG CAAATG G CTTATAGGTTTAATG GTATTG G AG TTAC ACAG
AATG TTCTCTATG AG AA
CCAAAAATTGATTG CC AAC CAATTTAATAG TG CTATTG G CAAAATT CAAG ACTCACTTTCTTCCAC AG
CAAGTG CA CTTG GA
AAACTTCAAG AT G TG GTCAACCAAAATG CA CAAG CTTTAAACACGCTTGTTAAACAACTTAG
CTCCAATTTTG GTG CAATTT
CAA G TG TTTTAAATG ATATCCTTG CAC G TCTTG AC AAAG TTG AG G CT G AAG T G CAAATTG
ATAG GTTG ATCACAGG CAG AC
TT CAAAG TTTG CAG AC ATATG T G ACTCAACAATTAATTA G AG CTG CAG AAATC AG AG
CTTCTG CTAATCTTG CT G CTACTAA
AAT G TCA G AG T G TG TACTTG G ACAAT CAAAAA G AG TTG ATTTTTGTG G AAA G G G
CTATCATCTTATG TCCTTCCCTCAGTCA
G CACCTCATG G TG TAG TCTTCTTG C AT G T G ACTTATGTCCCTG CACAAGAAAAG
AACTTCACAACTG CTCCTG CCATTTGTC
ATG ATG GAAAAGCACACTTTCCTCGTGAAG GTGTCTTTGTTTCAAATG G CACACACTG
GTTTGTAACACAAAG GAATTTTTA
TG AACCACAAATCATTACTACACACAACACATTTGTGTCTG GTAACTGTGATGTTGTAATAG G AATTG TCAAC
AACACAG TT
TAT G ATC CTTTG CAA CCT G AATTA G ACTCATTC AAG GAG G AG TTA G ATAAATATTTTAA G
AAT CATAC ATCAC C AG AT G TT G
ATTTAG GTG ACATCTCTG G CATTAATG CTTCAGTTGTAAACATTCAAAAAGAAATTG ACC G C CTCAATG
A G G TTG CCAAG A
ATTTAAAT G AATCTCTC ATC G ATCTCC AAG AA CTTG GAAAGTATG AG CAG TATATAAAAT G G
CCATG GTACATTTG G CTAG
GTTTTATAG CTG G CTTGATTG CCATAGTAATG GTG A CAATTA TG CTTTGCTGTATG ACC AGTTG
CTG TAGTTGT CTCAAG G G
CTGTTGTTCTTGTG GATCCTG CTG CAAATTTGATGAAG ACG ACTCTG AG CCAGTG CT CAAAG G AG
TCAAATTACATTACAC
ATAAACGAACTTATG GATTTGTTTATG AG AATCTTCACAATTGGAACTGTAACTTTGAAG CAAG GTG
AAATCAAGGATG CT
ACTCCTTCAGATTTTGTTCG CG CTACTG CAACGATACCG ATACAAG CCTCACTCCCTTTCG GATG G
CTTATTGTTG G CGTTG C
ACTTCTTG CTGTTTTTC AG AG CG CTTCCAAAATCATAACCCTCAAAAAG AG ATG G CAACTAG
CACTCTCCAAG G GTGTTC AC

TTTGTTTG CAACTTG CT G TTG TTG TTTG TAAC AG TTTACT CACAC CTTTTG CT CG TTG CT G
CT G G CCTTG AAG CC CCTTTTCT C
TAT CTTTATG CTTTAGTCTACTTCTTG CAG AG TATAAACTTTG TAAG AATAATAATG AG G CTTTG
GCTTTG CTG GAAATG CC
G TTC CAA AAACCC ATTACTTTATG AT G CCAACTATTTTCTTTG CTG G CATACTAATTGTTACG
ACTATTGTATACCTTACAATA
GTGTAACTTCTTCAATTG TCATTACTTCAGGTGATG G CACAACAAG T CCTATTTCTG AAC ATG A CTAC
CAG ATTG GTG GTTA
TACTGAAAAATG G G AATCTG G AG TAAAAG A CTG T G TTG TATTACACA G TTA CTTC ACTTC
AG ACTATTAC CAG CTG TA CTCA
ACT C AATT G A G TACAG ACACTG GTGTTG AACATGTTACCTTCTTCATCTACAATAAAATTGTTG ATG
A G CCTGAAGAACATG
TCCAAATTCACACAATCGACG GTTCATCCG G AG TTG TTAATC CAGTAATG G AACCAATTTATG
ATGAACCGACGACG ACTA
CTAG CGTGCCTTTGTAAG CACAAG CTG ATG AG TACG AACTTAT GTA CTCATTCG TTTCG G AAG AG
ACAG GTACGTTAATAG
TTAATAG CGTACTTCTTTTTCTTG CTTTCGTGGTATTCTTG CTAGTTACACTAG CCATCCTTACTG CG
CTTCGATTGTG TG CGT
ACT G CT G CAATATT G TTAACG T G AG T CTTG TAAAA CCTT CTTTTTAC GTTTA CTCTCG TG
TTAAAAAT CTGA ATTCTTCTAG A
G TTC CT G ATCTTCT G GTCTAAACG AACTAAATATTATATTAGTTTTTCTGTTTG G AACTTTAATTTTAG
CC ATG G CAGATTCC
AACG G TA CTATTACCG TTGAAG AG CTTAAAAAG CTCCTTGAACAATG GAACCTAGTAATAG
GTTTCCTATTCCTTACATG GA
TTTGTCTTCTACAATTTG CCTATG CCAACAG G AATAG GTTTTTGTATATAATTAAGTTAATTTTCCTCTG G
CTGTTATG G CCA
GTAACTTTAG CTTGTTTTGTG CTTG CTG CTGTTTACAGAATAAATTG G ATCACCG G TGGAATTG
CTATCGCAATG G CTTGTC
TTGTAG G CTT G AT GTG G CTCAG CTACTTCATTG CTTCTTTC AG ACTGTTTGCG CGTACG
CGTTCCATGTG GTCATTCAATCCA
GAAACTAACATTCTTCTCAAC GTG CCACTCCATGG C ACTATTCT G AC C AG ACC G CTTCTAG
AAAGTGAACTCGTAATCG GAG
CTG T G AT CCTT CGTG GACATCTTCGTATTG CT G GACACCATCTAG GACG CTGTG ACATCAAGG
ACCTG CCTAAAG AAAT CA
CTGTTG CTACATCACGAACG CTTTCTTATTACAAATTG G GAG CTTCG CAG CG TG TAG CAG G TG
ACT CAG GTTTTG CTG CAT
ACAGTCG CTACAG GATTG G CAACTATAAATTAAA CACAG ACCATTC CAG TAG CAGTGACAATATTG
CTTTG CTTG TAC AG T
AAG TGAC AACA G AT G TTTCAT CTCG TTG ACTTT CAG GTTACTATAG CAG AG
ATATTACTAATTATTATG AG G A CTTTTAAAG
TTTCCATTTG G AATCTTG ATTACATCATAAAC CTCATAATTAAAAATTTATCTAAGTCACTAACTG AG
AATAAATATTCTCAA
TTAG ATG AAG AG CAACCAATGG AG ATTG ATTAAACG AACATGAAAATTATTCTTTTCTTG G CACTG
ATAACACTCG CTACTT
G T G AG CTTTATCA CTACCAA G A GT G TG TTAG AG GTACAACAGTACTTTTAAAAG AACCTTG CT
CTTCTG G AA CATA CG AG G
G C AATTC ACC ATTTCATC CT CTAG CTGATAACAAATTTG CA CTG ACTTG CTTTAG CACTCAATTTG
CTTTTG CTTG TCCT G AC
G G CGTAAAACACGTCTATCAGTTAC GTG CCAGATCAGTTTCACCTAAACTGTTCATCAG ACAAG AG G AAG
TT CAAG AACTT
TACTCTCCAATTTTTCTTATTGTTG CG G CAATAGTGTTTATAACACTTTG CTTCACACTCAAAAG AAAG A
CAG AATG ATTGAA
CTTTCATTAATTGACTTCTATTTGTG CTTTTTAG CCTTTCTG CTATTCCTTGTTTTAATTATG
CTTATTATCTTTTG G TT CTCA CT
TG AACTG CAAG ATCATAATGAAACTTGTCACG CCTAAACG AACATG AAATTTCTTGTTTTCTTAG G
AATCAT CA CAA CTG TA
G CTG CATTTCACCAAG AATG TA GTTTAC AG TC ATG TACTTAACATCAACCATATG TAGTTGAT GACC
C G TG TCCTATTC ACTT
CTATTCTAAATG GTATATTAG AG TAG G AGCTATAAAATCAG CACCTTTAATTGAATTGTG CGTG G ATG
AG G CTG GTTCTAA
ATCACCCATTCAGTG CATCG ATATCG GTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTG CCAG G
AACCTAAATTG G
G TAG TCTTG TAGTG CGTTGTTCGTTCTATGAAG ACTTTTTAG AG TATCATG
ACGTTCGTGTTGTTTTAGATTTCATCTAAACG
AACAAACTAAATGTCTCTAAATG G ACC CCAAAATCAG CGAAATG CAC CC CG CATTACGTTTG GTG
GACCCTCAGATTCAAC
TG G CAGTAACCAGAATG GAG AACG CAGTG G G GC G CGATCAAAACAACGTCGG CCCCAAG
GTTTACCCAATAATACTG CGT
CTTG GTTCACCG CTCTCACTCAACATG GCAAG G AAGACCTTAAATTCC CTCG AG GACAAG G
CGTTCCAATTAACACCAATA
G CAGTCCAGATGACCAAATTG G CTACTACCGAAG AG CTACCAG ACGAATTCGTG GTG GTGACG
GTAAAATGAAAGATCTC
AG T CCAAG ATG GTATTTCTACTACCTAG G AACTG GG C CAGAAG CTG GACTTCCCTATG GTG
CTAACAAAGACG G CAT CATA
TG G GTTG CAACTG AG G GAG CCTTGAATACACCAAAAGATCACATTG G CACCCG
CAATCCTGCTAACAATGCTG CAATCGTG
CTACAACTTCCTCAAGG AACAACATTG CCAAAAG G CTTCTACG CAG AAG G GAG CAG AG G CG G
CAGTCAAG CCTCTTCTCG
TT CCTCATC ACG TAG T CG CAA CAG TT CAAG AAATTCAACTCCAG G C AG
CAGTAAACGAACTTCTCCTG CTAGAATG G CTG G
CAATGG CG GTG ATG CTG CTCTTG CTTTG CTG CTG CTTG ACAG ATTG AACCAG CTTG AG AG
CAAAATGTTTG GTAAAG G CCA
ACAACAACAAG G CCAAACTGTCACTAAG AAATCTG CT G CT G AG G CTTCTAAG AAG CCTCG G
CAAAAACGTACTG CCACTA
AAG CATACAATGTAACACAAG CTTTCG G CAG ACGTGGTCCAG AACAAACCCAAG GAAATTTTG G G G
ACCAG GAACTAATC
AGACAAG G AACTG ATTACAAACATTG G CC G CAAATTG CACAATTTG CCCCCAG CG CTTCAG
CGTTCTTCG G AATGTCGCG C
AUG GCATG G AAGTCACACCTTCG G G AACGTG GTTGACCTACACAG G TGCCATCAAATTG
GATGACAAAGATCCAAATTTC
AAAG ATCAAGTCATTTTG CTG AATAAG C ATATTG AC G CATA CAAAAC ATTCC CACCAA CAG AG
CCTAAAAAGG ACAAAAAG
AAG AA G G CTG AT G AAA CTCAAG CCTTACCG CAG AG ACAG AAG AAA CAG C AAA CTG TG A
CTCTTCTTCCTG CTG CAGATTT
G GATGATTTCTCCAAACAATTG CAACAATCCATG AG CAGTG CT G ACTC AACTCAG G CCTAAACTCATG
C A G ACCAC ACAAG
G CAGATG G GCTATATAAACG TTTTC GCTTTTC C GTTTACG ATATATAGTCTACT CTTG TGC AG
AATG AATT CTCG TAACTACA
TAG CACAAG TAG ATG TAG TTAACTTTAAT CTCA CATAG CAATCTTTAATC AG TG TG TAA CATTAG
G G AG GACTTG AAAG AG
CCACCACATTTTCACCGAGG CCACG CG G AGTA CG ATCG AG TGTACAGTG AACAATG CTAG G GAG
AG CTG CCTATATGG AA
GAG CCCTAATG TG TAAAATTAATTTTAG TAG TG CTATCCCCATGTGATTTTAATAG CTTCTTAG G AG
AATG NNNNNNNNN
NNNNNNNNNNNNNNNNNNNNNNNNNN

SEQ ID NO: 23 > M IG457_gp02 surface glycoprotein, from U K_M 1 G457 M FVFLVLLPLVSSQCVN LTTRTQLP PAYTNSFTRGVYYPDKVF RSSVLHSTQDLF LP FFSNVTWF
HAISGTNGTKRFDNPVLPFN

F RVYSSAN NCTFEYVSQ
PFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKIATPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTP
GDSSSGWTA
GAAAYYVGYLQPRTFLLKYN ENGTITDAVDCALDP LSETKCTLKSFTVE KG IYQTSNFRVQPTESIVRF
PNITN LCPFG EVFNATRF
ASVYAW N RKRISN CVADYSVLYNSASFSTF KCYG VS PTKLN DLCFTNVYADSFVIRG D EVRQIAPGQTG
KIADYNYKLPDDFTGC
VIAWNSN N LDSKVGG NY NYLYRLF R KS N LKP F ER D ISTE IYQAGSTPCNGVEG FNCYFPLQSYG
FQPTYGVGYQPYRVVVLSF EL
LHAPATVCG PKKSTN LVKNKCVNF NFNG LTGTGVLTESNKKF LPFQQFG R DI DDTTDAVR D PQTLE I
LDITPCSFGGVSVITPGT

ICASYQTQTNSH RRAR

DSTECSNLLLQYGSFCTQLNRALTG IAVE
QD KNTQEV FAQVKQIYKTP PI KD FG G F N FSQILP DPSKPSKRSF I E DLLF NKVTLADAG Fl KQYG DC LGD IAARDLICAQKFNG LTV
LP P LLTDE M IAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRF NG IGVTQNVLYENQKLIANQFNSAIG
KIQDSLSSTASAL
G KLQDVVNQNAQALNTLVKQLSSNFGAISSVLN DI LARLDKVEAEVQI DR LITG
RLQSLQTYVTQQLIRAAEIRASAN LAATKMS
ECVLGQSKRVDFCG KGYH LMSFPQSAPHGVVFLHVTYVPAQE KNFTTAPAIC H DG KAH F P R EGVFVS
NGTHW FVTQRN FY E P
QIITTHNTFVSGNCDVVIGIVNNTVYDPLQPELDSFKEELDKYFKNHTSPDVDLGDISGINASVVNIQKEIDRLNEVAK
NLNESLID
LQELG KYEQYI KWPWY IWLGFIAG LIAIVMVTI M
LCCMTSCCSCLKGCCSCGSCCKFDEDDSEPVLKGVKLHYT
SEQ ID NO: 24 >M W493681.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/hu nna n/USA/N M DO H-2021013232/2021, complete genome. [Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)], Californian B.1.427 lineage AAGGTTTATACCTTCCCAGGTAACAAACCAACCAACTTTCGATCTCTTGTAGATCTGTTCTCTAAACGAACTTTAAAAT
CTGT
GTGGCTGTCACTCGGCTGCATGCTTAGTGCACTCACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGA
GT
AACTCGTCTATCTTCTGCAGGCTG
CTTACGGTTTCGTCCGTGTTGCAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTG
TG ACCG AAAG G TAAGATGG AG AG CCTTGTCCCTG GTTTCAACGAG AAAACACACGTCCAACTCAGTTTG
CCTGTTTTACAG
GTTCGCGACGTG CTCGTACGTG GCTTTG GAGACTCCGTGGAGGAG GTCTTATCAGAGG
CACGTCAACATCTTAAAG ATG G
CACTTGTGGCTTAGTAGAAGTTGAAAAAGGCGTTTTGCCTCAACTTGAACAG
CCCTATGTGTTCATCAAACGTTCGGATGC
TCG AACTG CACCTCATG GTCATGTTATG GTTGAG CTG GTAG CAGAACTCGAAG G CATTCAGTACG
GTCGTAGTG GTG AGA
CACTTGGTGTCCTTGTCCCTCATGTGGGCGAAATACCAGTGGCTTACCGCAAGGTTCTTCTTCGTAAGAACG
GTAATAAAG
GAG CTG GTG G CCATAGTTACGG CG CCGATCTAAAGTCATTTGACTTAG G CGACGAG CTTG G
CACTGATCCTTATGAAG ATT
TTCAAGAAAACTG GAACACTAAACATAG CAGTGGTGTTACCCGTGAACTCATG CGTGAG CTTAACG GAG G G
G CATACACT
CGCTATGTCGATAACAACTTCTGTGGCCCTGATGGCTACCCTCTTGAGTGCATTAAAGACCTTCTAGCACGTGCTGGTA
AA
G CTTCATG CACTTTGTCC GAACAACTG G ACTTTATTGACACTAAG AG G G GTGTATACTGCTGCCGTG
AACATG AGCATGAA
ATTGCTTGGTACACGGAACGTTCTGAAAAGAG
CTATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTT
GACATCTTCAATG G G GAATGTCCAAATTTTGTATTTCCCTTAAATTCCATAATCAAGACTATTCAACCAAG G
GTTG AAAAG A
AAAAGCTTGATGGCTTTATGGGTAGAATTCGATCTGTCTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCT
TTC
AACTCTCATGAAGTGTGATCATTGTGGTGAAACTTCATGGCAGACG
GGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGG
CACTGAGAATTTGACTAAAGAAG GTG CCACTACTTGTG GTTACTTACCCCAAAATG
CTGTTGTTAAAATTTATTGTCCAG CA
TGTCACAATTCAGAAGTAGGACCTGAGCATAGTCTTGCCGAATACCATAATGAATCTG
GCTTGAAAACCATTCTTCGTAAG
G GTG GTCG CACTATTG CCTTTG GAG G CTGTGTGTTCTCTTATGTTG GTTG CCATAACAAGTGTG
CCTATTG G GTTCCACGTG
CTAGCGCTAACATAGGTTGTAACCATACAGGTGTTGTTGGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAAT
AC
TCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTGACTTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTT
TTC
TGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAGGTTTGGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGT
AAT
TTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCCTG
GAATATTGGTGAACAGAAATCAATACTGAGTCCTCTTTATGCA
TTTGCATCAGAGGCTGCTCGTGTTGTACGATCAATTTTCTCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTT
TACA
GAAGGCCGCTATAACAATACTAGATG
GAATTTCACAGTATTCACTGAGACTCATTGATGCTATGATGTTCACATCTGATTT
GGCTACTAACAATCTAGTTGTAATGGCCTACATTACAGGTGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATC
TTT
GGCACTGTTTATGAAAAACTCAAACCCGTCCTTGATTGGCTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAG
AC
G GTTGG GAAATTGTTAAATTTATCTCAACCTGTG CTTGTGAAATTGTCG GTG GACAAATTGTCACCTGTG
CAAAG GAAATT
AAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATAAATTTTTG GCTTTGTGTGCTGACTCTATCATTATTG GTG
GAG CTA
AACTTAAAGCCTTGAATTTAGGTGAAACATTTGTCACGCACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGA
AG
AAACTG G CCTACTCATG CCTCTAAAAG CCCCAAAAGAAATTATCTTCTTAG AG G G
AGAAACACTTCCCACAGAAGTGTTAA
CAG AG GAAGTTGTCTTGAAAACTGGTGATTTACAACCATTAGAACAACCTACTAG TGAAG CTGTTGAAG
CTCCATTG GTTG
GTACACCAGTTTGTATTAACGGGCTTATGTTGCTCGAAATCAAAGACACAGAAAAGTACTGTGCCCTTGCACCTAATAT
GA

TG GTAACAAACAATACCTTCACACTCAAAG G CG GTG CACCAACAAAG GTTACTTTTG G TG ATG AC
ACTG TG AT AG AAG TG C
AAG GTTACAAGAGTGTG AATATCACTTTTGAACTTG ATGAAAG G ATTG ATAAAG TACTTAATG AG
AAGTG CTCTG CCTATA
CAGTTGAACTCG G TAC AG AAG TAAAT G AG TTC G C CTG T GTTG TG G CAG AT G
CTGTCATAAAAACTTTG CAACC A G TATCTG
AATTACTTACACCACTG G G CATTG ATTTAG AT G AG T G GAG TAT G G CTACATA CTACTTATTTG
ATG AG TCTG GTG AG TTTAA
AUG GCTTCA CATATGTATTGTTCTTTTTACCCT CCAG ATG AG GATGAAG AAGAAG
GTGATTGTGAAGAAGAAG AGTTTG A
G CCATCAACT CAATATG AG TATG G TACT G AAG ATG ATTAC CAA G GTAAACCTTTG GAATTTG
GTG CCACTTCTG CTG CT CTT
CAACCTG AAGAAG AG CAAG AAG AAG ATTG GTTAG ATG ATG ATA GTCAACAAACTG TT G
GTCAACAAGACG G CAG TG AG G
ACAATCAGACAACTACTATTCAAACAATTGTTG AG GTTCAACCTCAATTAG AG AT G G AA CTTA C AC
CAG TTGTTCAGACTAT
TG AAGTGAATAGTTTTAGTGGTTATTTAAAACTTACTGACAATGTATACATTAAAAATG CAG A CATTGTG
GAAGAAG CTAA
AAAG GTAAAACCAACAGTG GTTGTTAATG CAG CCAATG TTTACCTTAAACATG GAG GAG GTGTTG CAG
GAG CCTTAAATA
AG G CTACTAACAATG CCATG CAA G TTG AATCTGATG ATTACATAG CTACTAATG G
ACCACTTAAAGTG G GTG G TAG TTG T
GTTTTAAG CG GACACAATCTTG CTAAACACTGTCTTCATGTTGTCGG CCCAAATGTTAACAAAG GTG
AAGACATTCAACTTC
TTAA G AG TG CTTATG AAAATTTTAATC AG CAC G AAG TTCTACTTG CA CCATTATTAT CAG CTG
GTATTTTTG GTG CTG A C CCT
ATA CATTCTTTA AG AG TTTG TG TA G ATA CTGTTC G CACAAATGTCTACTTAG CT G TCTTTG
ATAAAAATCTCTAT G A CAAACT
TGTTTCAAG CTTTTTG GAAATGAAG AG TG AAAAG CAAG TT G AACAAAAG ATCG CTG AG
ATTCCTAAAG A G G AA G TTAAG C
CATTTATAACTG AAAGTAAACCTTCAGTTG AACAG A G AAAAC AAG AT G ATAAG AAAATCAAA G CTT
G TG TTG AA G AAG TT
ACAACAACTCTG G AAGAAACTAAGTTCCTCACAGAAAACTTGTTACTTTATATTG ACATTAATG G
CAATCTTCATCCAGATT
CTG CCACTCTTGTTAGTG ACATTG ACATCACTTTCTTAAAG AAAG ATG CT CCATATATAGTG G GT G
ATG TTG TTCAAG AG G G
TGTTTTAACTG CTGTGGTTATACCTACTAAAAAG G CTG GTG G CACTACTG AAATG CTAGCGAAAG CTTT
G AG AAAA G TG CC
AACAGACAATTATATAACCACTTACCCG G GTC AG G GTTTAAATG GTTA CACTG TAG AG GAG G
CAAAGACAGTG CTTAAAA
AG T G TAAAAG TG CCTTTTACATTCTAC CAT CTATTATCTCTAATG AG AAG CAAG AAATTCTTG
GAACTGTTTCTTG G AATTTG
CG AG AAAT G CTTG CAC ATG C AG AAG AAACACG CAAATTAATG CCT G T CT G TG TG
GAAACTAAAG CCATAGTTTCAACTATA
CAG CGTAAATATAAG G GTATTAAAATACAAG AG G GTGTG GTTGATTATG GTG CTAG
ATTTTACTTTTAC ACCAG TAAAA C A
ACT G TAG CGTCACTTATCAACACACTTAAC GATCTAAATGAAACTCTTGTTACAATG CCACTTG G
CTATGTAACACATGG CT
TAAATTTG GAAG AAG CTG CT C G G TATAT G AG ATCTCT CAAAGTG CC AG CTAC AGTTTCT G
TTTCTT CACCT G ATG CTGTTAC
AG C G TATAATG GTTATCTTACTTCTTCTTCTAAAACACCTGAAG AACATTTTATTG AAACC ATCT CACTT
G CT G G TTCCTATA
AAG AUG GTCCTATTCTG G ACAATCTACACAACTAG GTATAG AATTTCTTAAG AG AG
GTGATAAAAGTGTATATTACACTA
GTAATCCTACCACATTCCACCTAG ATG GTGAAGTTATCACCTTTGACAATCTTAAG ACACTT CTTT CTTTGAG
AG AAGTG AG
GACTATTAAG G TG TTTACAA CA GTA GACAACATTAACCTCCACACG CAAGTTGTG GACATGTCAATG
ACATATG G A CAA CA
GTTTG GTCCAACTTATTTG GATG GAG CTG ATGTTACTAAAATAAAACCT CATAATTCAC ATG AA G G
TAAAACATTTT ATG TT
TTACCTAATG ATG A CACTCTACG TG TT G AG G CTTTTG AG TACTACCACA CAACTG ATCC TAG
TTTTC TG G G TAG GTACATGT
CAG CATTAAATCACACTAAAAAGTG GAAATACCCACAAGTTAATG GTTTAACTTCTATTAAATG GG CAG
ATAACAACT G TT
ATCTTG CCACTG CATT G TTAA CACT CCAAC AAATA G AG TTG AAG TTTAATCC ACCTG
CTCTACAAG ATG CTTATTACAG AG C
AAG G G CTG GTGAAG CTG CTAACTTTTGTG CACTTATCTTAGCCTACTGTAATAAG ACAG TA G GTG
AG TTAG GT G AT G TTAG
AG AAA CAATG AG TTACTTG TTTCAAC ATG CCAATTTAGATTCTTG CAAAAGAGTCTTGAACGTG
GTGTGTAAAACTTGTG G
ACAACAG CA G ACAAC CCTTAAG G G TG TAG AAG CTGTTATGTACATG G G CACACTTTCTTATG
AACAATTTAAG AAA G GTGT
TCAGATACCTTGTACGTGTG GTAAA CAA G CTACAAAATATCTAGTACAACAG G AG TCACCTTTTGTTATG
ATGTCAGCACCA
CCTG CT CAG TATG AA CTTAA G CAT G GTACATTTACTTGTG CTAG TG AG TACACTG
GTAATTACCAGTGTG GT CACTATAAAC
ATATAACTTCTAAAGAAACTTTGTATTG CATAG AC G GTG CTTTACTTACAAAGTCCTCAGAATACAAAG
GTCCTATTACG GA
TGTTTTCTACAAAGAAAACAGTTACACAACAACCATAAAACCAGTTACTTATAAATTG GATG G TG TTG TTT G
TA CAG AAATT
G AC CCTAAG TTG G ACAATTATTATAAG A AAG ACAATT CTTATTT CACAG AG CAAC CAATT G
ATCTTG TA CC AAACC AACC AT
ATCCAAACG CAAG CTTCGATAATTTTAAGTTTG TATGTGATAATATCAAATTTG CTG
ATGATTTAAACCAGTTAACTG GTTA
TAA G AAAC CTG CTTCAA G AG A G CTTAAAGTTACATTTTTCCCTGACTTAAATG GTGATGTG GTG G
CTATTGATTATAAACAC
TAC ACAC C CTCTTTTAAG AAA G GAG CTAAATTGTTACATAAACCTATTGTTTG G CATGTTAACAATG
CAACTAATAAAG C CA
CGTATAAACCAAATACCTG GT G TATAC G TTGTCTTTGG AG CAC AAAACC AG TT G AAAC
ATCAAATTC G TTTG ATG TACTG AA
G T CAG AG G AC G CG C AG G G AATG G ATAATCTTG T CT G CG AAG AT CTAAA ACCAG
TCTCTG AA G AAG TAG TG GAAAATCCTA
CCATACAG AAAGACGTTCTTG AG TG TAATGTG AAAACTACCG AAG TT GTAG G AG
ACATTATACTTAAACC AG CAAATAATA
G TTTAAA AATTA CAG AAG AG GTTG G C CAC ACA G AT CTAATG G CTG
CTTATGTAGACAATTCTAGTCTTACTATTAAGAAAC
CTAATG AATTAT CTAG AG TATTAG GTTTGAAAACCCTTG CTACTCATG GTTTAG CT G
CTGTTAATAGTGTCCCTTG G G ATAC
TATA G CT AATTATG CTAAG CCTTTTCTTAACAAAGTTGTTAGTACAACTACTAACATAGTTACACGG
TGTTTAAACCGTGTTT
G TA CTAATTATATG CCTTATTTCTTTACTTTATTG CTA C A ATTG TG TA CITTTA CTA G AA G TA
CAA ATTCTA G AATTAAA G CAT
CTATG CCGACTACTATAG CAAAGAATACTG TTAAG AG TGTCG G TAAATTTTGTCTAG AG
GCTTCATTTAATTATTTGAAGTC
ACCTAATTTTTCTAAACTGATAAATATTATAATTTG GTTTTTACTATTAAGTGTTTG CCTAG
GTTCTTTAATCTACTCAACCG C
TG CTTTAG GT GTTTTAATGTCTAATTTAG G CATG CCTTCTTACTG TACT G GTTACAG AG AAG G
CTATTTG AACTCTACTAATG
TCACTATTG CAACCTACT G TA CTG GTT CTATACCTT G TAG TGTTTG TCTTAGTG
GTTTAGATTCTTTAG ACACCTATCCTTCTT

TAG AAACTATACAAATTACCATTT CAT CTTTTAAAT G G GATTTAACTGCTTTTG G CTTAGTTG CA G
AG TG GTTTTTG GCATAT
ATTCTTTTCACTAG G TTTTTCTATG TA CTTG GATTG G CT G CAATCATG CAATTG TTTTTC AG
CTATTTTG CAGTACATTTTATT
AG TAATT CTTG G CTTATGTG GTTAATAATTAATCTTGTACAAATG GCCCCGATTTCAG CTATG
GTTAGAATGTACATCTTCT
TT G C AT CATTTTATTAT GTATG G AAAAGTTATGTG CATG TT G TAG AC G G TTG TAATTCAT
CAACTTG TAT G AT G TG TTA CAA
AC G TAATAG AG C AA CAA G AG TC G AATG TACAACTATTG TTAATG GTGTTAGAAG GT
CCTTTTAT G TCTATG CTAATG GAG G
TAAAGG CTTTTG CAAACTACACAATTG G AATTGTGTTAATTGTGATACATTCTGTG CTG G TA G TAC
ATTTATTAG TG ATG AA
GTTG CG AG AG ACTT G TCA CTACA G TTTAAAAG ACCAATAAATCCTACTG
ACCAGTCTTCTTACATCGTTGATAGTGTTACAG
TG AAGAATG GTTCCATCCATCTTTACTTTGATAAAG CTG GTCAAAAGACTTATG AAA G A CATT CTCT
CTCTC ATTTTG TTAAC
TTAG ACAACCTG A G AG CTAATAACACTAAAG GTTCATTG CCTATTAATGTTATAGTTTTTGATG
GTAAATCAAAATGTG AAG
AATCATCTG CAAAATCAG C GT CTG TTTACTACA G TCAG CTTAT G T GT CAACCT ATA CT G
TTACTAG ATCAG G CATT AG TG TC
TG ATG TT G GTGATAGTG CG G AAG TT G CAG TTAAAATG TTTG AT G
CTTACGTTAATACGTTTTCATCAACTTTTAACGTACCA
ATG GAAAAACTCAAAACACTAGTTG CAACTG C AG AAG CTG AACTTG CAAA G AATG TG T CCTTAG
A CAATGT CTTAT CTACT
TTTATTTCAG C AG CT C G G CAAG G G TTTG TT G ATT CAG AT G TA G AAACTAAAG ATG
TTG TTG AATGTCTTAAATTGTCACATC
AATCTGACATAG AAGTTACTG G CG ATAGTTGTAATAACTATATG CT CACCT ATAAC AAAG TTG
AAAACATG ACACC CC GTG
ACCTTG GTG CTTGTATTGACTGTAGTG CG CGTCATATTAATG CG CAG G TAG
CAAAAAGTCACAACATTGCTTTG ATATG GA
AC G TTAAAG ATTT CAT G TCATTG T CTG AAC AACTAC G AAAACAAATAC G TAG TG CTG
CTAAAAAGAATAACTTACCTTTTAA
G TTG AC ATG T G CAACTACTAG ACAAG TT G TTAATGTTGTAACAAC AAAG ATAG CA CTTAA G G
GTG GTAAAATTGTTAATAA
TTG GTTG AAG CAGTTAATTAAAGTTACACTTGTGTTCCTTTTTGTTG CTG CTATTTTCTATTTAATAA CAC
CTG TT CATGTC AT
GTCTAAACATACTGACTTTTCAAGTGAAATCATAG GATACAAG G CTATTGATG GTG
GTGTCACTCGTGACATAG CAT CTAC
AG ATACTTG TTTTG CTAACAAACATG CTG ATTTTG A CACAT G GTTTAG CCAGCGTG GTGG TAG
TTATACTAAT G ACAAAG CT
TG CCCATTGATTG CTG CAGTCATAAC AAG AG AAGTG G GTTTTG TCGTG CCTG GTTTG CCTG G
CACGATATTACG CACAACT
AATG GT G ACTTTTT G CATTTCTTACCTAG A G TTTTTA G TG C AG TTG G TAACAT CTG TTACA
CAC CATCAAAACTTATAG A GTA
CA CT G ACTTTG C AACATC AG CTTGTGTTTTG G CT G CT G AATG TACAATTTTTAAAG ATG
CTTCTG GTAAGCCAGTACCATAT
TGTTATGATACCAATGTACTAGAAG GTTCTGTTG CTTATGAAAGTTTACG CCCT G ACA CAC G TTATG T
G CT CATG GATG G CT
CTATTATTCAATTTCCTAACACCTACCTTG AAG GTTCTGTTAG AG T G GTAACAACTTTTGATTCTG AG
TACTG TAG G CAC G G
CACTTG TG AAAG ATCAG AA G CTG GTG TTTGTGTATCTACTAGTG G TA G ATG G G TA CTTAA C
AAT G ATTATTACAGATCTTTA
CCAG G AG TTTTCTG TG G TG TA G ATG CTG
TAAATTTACTTACTAATATGTTTACACCACTAATTCAACCTATTG GTG CTTTG GA
CATATCAG CATCTATAGTAG CTG GTGGTATTGTAG CTATCGTAGTAACATG CCTTG C CTACTATTTTATG
AG GTTTAG AAG A
G CTTTTGGTG AAT ACAGTCATG TAG TTG CCTTTAATACTTTACTATTC CTTATG TCATTC ACTG
TACTCTG TTTAAC ACCAG TT
TACTCATTCTTACCTG G TG TTTATTCT G TTATTTACTT G TACTTG A CATTTTATCTTACTAATG
ATGTTTCTTTTTTAG CACATA
TT CAG T G G AT G G TTAT G TTCA CACCTTTAG TACCTTTCTG G ATAACAATTG
CTTATATCATTTGTATTTCCACAAAG CATTTCT
AUG G TT CTTTACTAATTA CCTAAAG AG AC G TG TA G TCTTTAAT G GTGTTTCCTTTAGTACTTTTG
AAGAAG CTGCG CTGTG
CAC CTTTTTG TTAAATAAAG AAATGTATCTAAAGTTG C G TA G TG ATGTG CTATTACCTCTTACG
CAATATAATAG ATACTTA
G CTCTTTATAATAAGTACAAGTATTTTAGTGG AG CAATG G ATACAACTAG CTAC AG AG AAG CTG
CTTGTTGTCATCTCG CA
AAG G CTCTCAATGACTTCAGTAACTCAG G TTCT G AT G TT CTTTACC AACC ACC ACAAAC
CTCTATCACCTCAG CTGTTTTG CA
G AG TG GTTTTAGAAAAATG G CATTCCCATCTG GTAAAG TT G AG G GTTGTATG GTACAAG
TAACTTGTG GTACAACTACACT
TAACGGTCTTTG G CTTGATGACGTAGTTTACTGTCCAAG ACATGTG ATCTG CACCTCTG AAGACATG
CTTAACCCTAATTAT
G AA G ATTTACT CATTC G TAA G TCTAATCATAATTTCTT G G TACA G G
CTGGTAATGTTCAACTCAG G GTTATTG G AC ATTCTA
TG CAAAATTGTGTACTTAAG CTTAAG GTTGATACAG CCAATCCTAAGACACCTAAGTATAAGTTTGTTCG
CATTCAACCAG G
ACAG ACTTTTTCAGTGTTAG CTTGTTACAATG GTTCACCATCTG GTGTTTACCAATGTG CTATG AG
GCCCAATTTCACTATTA
AG G G TT CATT CCTTAATG GTTCATGTG G TAG TG TTG G TTTTAACATAG ATTATG A CTG TG
TCTCTTTTTG TTACAT G C AC C AT
ATG GAATTACCAACTG G AG TTCATG CTG G CACAGACTTAGAAG GTAACTTTTATG G ACCTTTTGTT G
AC AG GCAAACAG CA
CAAG CAG CTG G TACG GACACAACTATTACAGTTAATGTTTTAG CTTGGTTGTACG CTG CTGTTATAAATG
GAG ACAG GTG G
TTTCTCAATCG ATTTACCACAACTCTTAATGACTTTAACCTTGTG G CTATG AAGTACAATTATG AACCT
CTAACA CAA G ACCA
TG TTG A C ATA CTAG G ACCTCTTTCTG CTCAAACTG G AATTG CCGTTTTAG ATATGTGTG
CTTCATTAAAAGAATTACTG CAA
AATG GTATGAATG G ACGTACCATATTG G GTAG TG CTTTATTAG
AAGATGAATTTACACCTTTTGATGTTGTTAGACAATG CT
CAG GTGTTACTTTCCAAAGTG CAGTGAAAAGAACAATCAAG G G TACAC AC CACT G G TTG TTACTC
AC AATTTTG ACTT CACT
TTTAG TTTTAGTCCAG AG TACTC AATG GTCTTTGTTCTTTTTTTTGTATGAAAATGCCTTTTTACCTTTTG
CTATG G GTATTAT
TG CTATG TCTG CTTTTG CAATG ATGTTTGTCAAACATAAG CATG CATTTCTCTGTTTGTTTTTGTTAC
CTTCTCTTG CCACTG
TAG CTTATTTTAATATG GTCTATATG CCTGCTAGTTG G GTGATG CGTATTATG AC ATG G TTG G
ATATG GTTGATACTAGTTT
GTCTG GTTTTAAG CTAAAA G A CTG T GTTATG TATG CAT CA G CT G TA G TG TTA CTAAT
CCTTATG A CAG CAA G A ACTG T G TAT
GATGATG GTG CTAG GAG AGTGTG G ACACTTATGAATGTCTTG ACACTCGTTTATAAAGTTTATTATG
GTAATG CTTTAG AT
CAAG CCATTTCCATGTG G G CTCTTATAATCTCTGTTACTTCTAACTACTCAG G TG TAG TTACAACT G
TCATG TTTTT G G CC AA
AG G TATTGTTTTTAT G TG TG TTG AG TATTG CC CTATTTTCTTCATAACT G G TAATAC ACTT CA
G TG TATAATG CTAGTTTATT
GTTTCTTAG G CTATTTTTGTACTTGTTACTTTG G CCTCTTTTGTTTACTCAACCG CTACTTTAG ACT G
ACT CTTG GTGTTTATG

ATTACTTAGTTTCTACACAG G AG TTTAG ATATATG AATTCA CAG G GACTACTCCCACCCAAGAATAG
CATAGATG CCTTC AA
ACTCAACATTAAATTGTTGG GTGTTG GTGG CAAACCTTGTATCAAAGTAG CCACTGTAC AG TCTAAAAT
GTC AG ATG TAAA
GTG CAC ATCAG TAG T CTTA CTCT C AG TTTTG CAACAACTCA G AG TAG AAT CATC
ATCTAAATTG TG G G CT C AAT G TG T CCAG
TTACACAATG AC ATTCT CTTAG CTAAAGATACTACTG AA G CCTTTGAAAAAATG G TTTC ACTACTTT
CT G TTTTG CTTTC CAT
G C AG G GTG CT G TAG ACATAAACAAG CTTT GT G AAG AAATG CTG G A CAA CAG G G CAA
CCTTA CAAG CTATAG CCTCA G AG T
TTAG TT CCCTT CCAT CATAT G CAG CTTTTG CTACTG CTCAA G AAG CTTAT G AG CAG G CTG
TT G CTAATG GTGATTCTG AAGT
TGTTCTTAAAAAGTTGAAG AAGTCTTTG AATGTG G CTAAATCTG AATTTG ACC G TG ATGCAG CCATG
CAACGTAAGTTG GA
AAAG ATG G CTG ATCAAG CTATG A CCCAAATG TATAAACA G G CTAG AT CT G AG G ACAA G
AG G G CAAAAGTTACTAGTG CTA
TG CAGACAATG CTTTTCACTATG CTTAGAAAG TT G GATAATGATG CACTCAACAACATTATCAACAATG
CAAG AG ATG G TT
GTGTTCCCTTGAACATAATACCTCTTACAACAG CAG CCAAATTAATG GTTGTCATACCAG
ACTATAACACATATAAAAATAC
GTGTGATGGTACAACATTTACTTATG CAT CAG CATTGTG G GAAATCCAACAG GTTGTAG AT G CAG
ATAGTAAAATTGTTCA
ACTTAGTGAAATTAGTATG GACAATTC A CCTAATTTAG CATG G CCTCTTATTGTAACAG CTTTAAG G G
CCAATTCTG CTGTC
AAATTAC AG AATAATG AG CTTA G TC CTG TT G CACTACGACAGATGTCTTGTG CT G CCG
GTACTACACAAACTG CTTG CACT
G AT G ACAATG CGTTAG CTTACTACAACACAACAAAG G G AG G TAG GTTTGTACTTG
CACTGTTATCCG ATTTACAGGATTTG
AAATGG G CTAG ATTC CCTAAG AG T G AT G G AACTG GTACTATCTATACAG AACTG G AA
CCACCTTG TAG GTTTG TTAC AG AC
ACACCTAAAG GTCCTAAAGTGAAGTATTTATACTTTATTAAAG G ATTAAACAAC CTAAATAG A G GTATG G
TA CTTG G TAG T
HAG CTG CCA C AG TAC GTCTACAAG CTG GTAATG CAAC AG AAG TG CCTG
CCAATTCAACTGTATTATCTTTCTGTG CTTTTG
CTG TAG ATG CTG CTAAAG CTTACAAAGATTATCTAG CTAGTG G G GG AC AACCAATCACTAATTG TG
TTAAG ATG TTG TG TA
CAC ACACTG GTACTG GTCAG G CAATAACAGTTACACCG GAAG CC AATATG G AT CAAG AATCCTTTG
GTG GTG CATCG TG TT
G T CT G TACTG CCGTTG CC ACATA G ATC ATCCAAATC CTAAAG G ATTTTGTGACTTAAAAG
GTAAGTATGTACAAATACCTAC
AACTTGTG CTAATG AC CCTG TG GGTTTTACACTTAAAAACACAGTCTGTACCGTCTG CG GTATGTG
GAAAG GTTATG G CTG
TAG TTG TG AT CAACTCCG CG AACCCATG CTTCAGTCAG CTG ATG CA CAATC GTTTTTAAACG G
GTTTG CG GTGTAAGTG CA
G CCCGTCTTACACCGTG CG G CACAG G CACTAGTACTGATGTCGTATACAG G G CTTTTG
ACATCTACAATG ATAAAG TAG CT
G GTTTTG CTAAATTCCTAAAAACTAATTGTTGTCG CTTCCAAGAAAAG G AC G AAG AT G
ACAATTTAATTG ATTCTTACTTTG
TAG TTAA G AG A CACACTTTCTCTAACTAC CAACAT G AAG AAACAATTTATAATTTACTTAAAG ATT G
TCC AG CT G TTG CTAA
ACATGACTTCTTTAAGTTTAG AATAGACG GTG ACATG G TA CCACATATAT C ACG T CAACG
TCTTACTAAATACACAATG G CA
G AC CTCG TCTATG CTTTAAG G CATTTTGATGAAG GTAATTGTG ACACATTAAAAG
AAATACTTGTCACATACAATTGTTG TG
ATG ATG ATTATTTCAATAAAAAG G A CTG GTATG ATTTTG TAG AAAA CCCAG ATATATTAC G
CGTATACG CCAACTTAG GTG
AACGTGTACG CC AAG CTTT G TTAAAAAC AG T ACAATT CTG T G ATG CCATGCGAAATG CTG
GTATTGTTG GTGTACTG ACAT
TAG ATAATCAAGATCTCAATG G TAACTG GTATGATTTCG GTGATTTCATACAAACCACGCCAG GTAGTG G
AG TT CCTG TTG
TAG ATTCTTATTATTCATTGTTAATG CCTATATTAAC CTT G ACC AG G GCTTTAACTG CAG AG T
CACAT G TT G ACACTG ACTTA
ACAAAG CCTTACATTAAGTGG G ATTTGTTAAAATATGACTTCACG G AAG AG AG
GTTAAAACTCTTTGACCGTTATTTTAAAT
AUG GG ATCAG ACATACCACCCAAATTGTGTTAACTGTTTG G ATGACAGATG CATTCTGCATTGTG
CAAACTTTAATGTTTT
ATTCTCTACAGTGTTCCCACTTACAAGTTTTG GAC C ACTA G TG A G AAAAATATTTG TTG AT G G TG
TTC CATTTG TAG TTTCAA
CTG G ATA CCACTTCAG AG AG CTAG GTGTTGTACATAATCAG G AT GTAAACTTAC ATAG
CTCTAGACTTAGTTTTAAG G AAT
TACTTGTGTATG CT G CT G ACC CTG CTATG CACG CTG CTTCTG GTAATCTATTACTAG ATAAACG
CACTACGTG CTTTTCAG TA
G CTG CA CTTA CTAAC AATG TTG CTTTTCAAACTGTCAAACCCG GTAATTTTAACAAAGACTTCTATG
ACTTTG CTGTGTCTAA
G G GTTTCTTTAAG G AAG G AA GTTCTG TTG AATTAAAACACTTCTT CTTT G CTC AG G ATG
GTAATG CTG CTATC AG CGATTAT
GACTACTATCGTTATAATCTACCAACAATGTGTGATATCAGACAACTACTATTTGTAGTTGAAGTTGTTGATAAGTACT
TTG
ATTGTTACGATG GTG G CTGTATTAATG CTAACCAAGTCATCGTCAACAACCTAG ACAAATCAG CTG
GTTTTCCATTTAATAA
ATG G G GTAAG G CTAGACTTTATTATGATTCAATG AG TTAT G AG G ATCAAGATG CACTTTTCG
CATATACAAAACGTAATGT
CAT C CCTACTATAACT CAAATG AATCTTAA G TAT G CCATTAGTG CAAAGAATAG AG CTCG CAC C
GTAG CTG GTGTCTCTATC
TGTAGTACTATG ACCAATAGAC AG TTT CATCAAAAATTATTG AAATCAATAG CC G CCACTAG AG GAG
CTACTG TAG TAATT
G GAACAAG CAAATTCTATG GTG GTTG G CACAACATGTTAAAAACTGTTTATAGTG ATG TAG AAAACCCT
CACCTTATG G CT
TG G GATTATCCTAAATGTG ATA G AG CC ATG CCTAACATG CTTAG AATTATG G C CTCACTTG
TTCTTG CT CG CAAACATACAA
CGTGTTG TAG CTTGTCACACCGTTTCTATAGATTAG CTAATG AG TG TG CTCAAG TATTG AG TG
AAATGG TCATGTGTG G CG
GTTCACTATATGTTAAACCAG GTG G AAC CTCATCAG G AG AT G CCACAACTGCTTATG
CTAATAGTGTTTTTAACATTTGTCA
AG CTGT CACG G CCAATGTTAATGCACTTTTATCTACTGATG GTAACAAAATTG CC G ATAA G TAT G
TC CG CAATTTA C AAC AC
AG ACTTTATG AG TG TCT CTATAG AAATAG AG AT G TT G ACA CA G ACTTTGTGAATG
AGTTTTACG CATATTTG CGTAAACATT
TCTCAATGATG ATACTCTCTG ACG ATG CTGTTGTGTGTTTCAATAG CACTTATG CATCTCAAG GTCTAGTG
G CTAGCATAAA
G AA CTTTAAGTCA GTT CTTTATTATCAAAA CAATG TTTTTATG TCTG AA G CAAAATGTTG G ACTG
AGA CTG ACCTTA CTAAA
G GACCTCATG AATTTTG CTCTCAACATACAATG CTAGTTAAACAG G G TG AT G ATTAT G TG TAC
CTTCC TTACC CAGAT CCAT
CAAG AATCCTAG CC G CC GG CTG TTTTG TAG ATGATATCGTAAAAA CAG ATG GT ACACTTATG
ATTG AACGGTTCGTGTCTT
TAG CTATAG AT G CTTACCC ACTTA CTAAA CATCCTAATC AG G AG TAT G CT G ATG
TCTTTCATTTG TA CTTACAATACATAAG A
AAG CTAC ATG AT G AG TTAAC AG G A CACAT GTTAG A CATG TATTCTG TTATG
CTTACTAATGATAACACTTCAAG GTATTG G

GAACCTG AGTTTTATG AG G CTATGTACACACCG CATACAGTCTTACAG G CTGTTG G GG CTTGTGTT
CTTTGCAATTCAC AG A
CTTCATTAAGATGTG GTG CTTG CATACGTAG ACCATTCTTATGTTGTAAATG CTGTTACG AC CAT
GTCATATC AAC ATC ACAT
AAATTAGTCTTGTCTGTTAATCCGTATGTTTG CAATG CTCTAG GTTGTGATGTCACAG
ATGTGACTCAACTTTACTTAG GAG
GTATG A G CTATTATTGTAAATCACATAAACCACCCATTAGTTTTCCATTGTGTG CTAATG GACAAGTTTTTG
GTTTATATAAA
AATACATGTGTTG GTAGCG ATAATGTTACTG ACTTTAATG CAATTG CAA CATG T G ACTG G ACAAATG
CTG GTG ATTACATTT
TAG CTAACACCTG TACT G AAAG ACT CAA G CTTTTTG CAG C AG AAAC G CTCAAAG CTACTG AG
G AG AC ATTTAAACTGT CTT
ATG GTATTG CTACTG TACG TG AAG T G CT GTCT G A CA G AG AATTACATCTTT CATG G G AA
GTTG GTAAACCTAG ACCACCAC
TTAACCG AAATTATGTCTTTACTG GTTATCGTGTAACTAAAAACAGTAAAGTACAAATAG G AG
AGTACACCTTTG AAAAAG
GT G ACTATG G TG AT G CTG TTG TTTA CCG AG GTACAACAACTTACAAATTAAATGTTG
GTGATTATTTTGTG CTGACATCACA
TACAGTAATG CC ATTAA GTG C ACCTACACTA GTG CCACAA G AG CACTATGTTAGAATTACTG G
CTTATACCCAACACTCAAT
ATCTCATATGAGTTTTCTAG CAATGTTG CAAATTATCAAAAG GTTG GTATG CAAAAG TATTCTAC ACT
CCAG G G ACC ACCTG
GTACTG GTAAGAGTCATTTTG CTATTG G CCTAG CTCT CTACTACCCTTCT G CT CG CATAGT GTATAC
AG CTTG CTCTCATG CC
G CTGTTG AT G CACTATGTG AG AAG G CATTAAAATATTTG CCTATAG ATAAAT GTAG TAG
AATTATACCT G CACGTG CT CGT
GTAG AG TGTTTTG ATAAATTCAAAGTG AATTC AA CATTAG AACAGTATGT CTTTTGTACTG TAAAT G
CATTG CCTG A G ACG A
CAG CAGATATAGTTGTCTTTGATGAAATTTCAATG G CCACAAATTATG ATTTGAGTGTTGTCAATG
CCAGATTACGTG CTAA
G CACTATGTGTACATTG G C G ACCCTG CT CAATTACCTG CAC CACG CAC ATTG CTAACTAAG GG
CACACTAGAACCAG AATA
TTTCAATTC AG TGTG TAG ACTTATGAAAA CTATAG GTCCAGACATGTTCCTCG G AACTTGTCG G
CGTTGTCCTG CTG AAATT
GTTG AC ACTGT G AG TG CTTTG G TTTATGATAATAAG CTTAAAG CACATAAAGACAAATCAG
CTCAATG CTTTAAAATGTTTT
ATAAGG GTGTTATCACG C ATG AT GTTT CATCT G CAATTAAC AG G CCACAAATAG G CGTG GTAAG
A G AATT CCTTACACG TA
ACC CTG CTTG G AG AAAAG CT GTCTTTATTT CAC CTTATAATTCACAG AATG CTGTAG CCTCAAAG
ATTTTG G GA CTA CCAAC
TCAAACTGTTG ATTC ATC AC AG G G CTCAGAATATGACTATGTCATATTCACTCAAACCACTG AAA CAG
CT CACT CTTG TAAT
GTAAACAG ATTTAATG TTG CTATTACC A G AG C AAAAG TAG G CATACTTTG CATAATGT CT G
ATAG AG ACCTTTATG A CAAG
TT G C AATTTAC AAGTCTT G AAATTC CACG TAG G AATGTG G CAACTTTA CAA G CTG AAAAT
GTAAC AG G A CTCTTTAAA G ATT
GTAGTAAG GTAATCACTG G GTTACATCCTACACAG G
CACCTACACACCTCAGTGTTGACACTAAATTCAAAACTG AAGGTT
TAT G TG TTG ACATACCTG G CATACCTAAG G A CATG AC CTATAG AAG ACTCATCTCTATG ATG G
GTTTTAAAATGAATTATCA
AGTTAATGGTTACCCTAACATGTTTATCACCCG CGAAGAAGCTATAAGACATGTACGTG CATG GATTG GCTTCG
ATGTCG A
G G G GTGTCATG CTA CTAG AG AAG CTGTTG GTACCAATTTACCTTTACAG CTAG G TTTTTCTAC AG
GTGTTAACCTAGTTG CT
GTACCTACAG GTTAT G TT G ATA CACCTAATAATACAG ATTTTTC CAGAGTTAGTG CTAAACC ACC G
CCTG G AG AT CAATTTA
AACACCTCATACCACTTATGTACAAAG G ACTTC CTTG GAATG TAG TG
CGTATAAAGATTGTACAAATGTTAAGTGACACACT
TAAAAATCTCTCTG ACAG AG TCGTATTTGTCTTATG GG CACATG G CTTTG
AGTTGACATCTATGAAGTATTTTGTGAAAATA
G GACCTG AG CG CACCTG TT GTCTAT GT G ATAGACGTG CC ACATG CTTTTCCACTG CTTCAG
ACACTTATG CCTG TTG G CATC
ATTCTATTG GATTTG ATTACGTCTATAATCCG TTTATGATTGATGTTCAACAATG G G GTTTTACAGG
TAACCTACAAAG CAA
CCAT G AT CTGTATTG TCAAG TCCATG GTAATG CACATGTAG CTAGTTGTGATG CAATCATGACTAG
GTGTCTAG CTGTCCAC
G AG TG CTTTGTTA AG CGTGTTG ACTGG ACTATTG AATATCCTATAATTG GTG ATGAACTG
AAGATTAATG CGG CTTGTAG A
AAG GTTCAACACATG GTTGTTAAAG CTG CATTATTAG CAG AC AAATT CCCAG TTCTTCAC G ACATTG
GTAACCCTAAAG CTA
TTAAGTG TGTACCTCAAG CT G AT GTAG AATG G AAGTTCTATG AT G CACAG CCTTGTAGTGACAAAG
CTTATAAAATAGAAG
AATTATTCTATT CTTATGCC ACACATTCTG ACAAATTC AC AG ATGGTGTATG CCTATTTTG G AATTG
CAATGTCG ATAG ATAT
CCTG CTAATTCCATTGTTTGTAGATTTGACACTAG AGTG CTATCTAACCTTAACTTG CCTG GTTGTGATG
GTG G CAGTTTGT
ATGTAAATAAACATG CATTCCACACACCAG CTTTTG ATAAAAGTG
CTTTTGTTAATTTAAAACAATTACCATTTTTCTATTAC
TCTG ACAGTCCATGTG AGTCTCATG G AA AAC AAG TAGT GTCA G ATATAG ATTATG
TACCACTAAAGTCTG CTAC GTG TATA
ACACGTTGCAATTTAG GTG GTG CT GTCT GTAG AC ATC ATG CTAATG AGTAC AG ATTGTAT CTC G
AT G CTTATAACATG ATG
ATCTCAG CTG G CTTTAG CTTGTG G GTTTACAAACAATTTGATACTTATAACCTCTG G AA CACTTTTA
CAA G ACTTC AG A G TTT
AGAAAATGTG G CTTTTAATGTTGTAAATAAG G G AC ACTTT G AT G GACAACAG G
GTGAAGTACCAGTTTCTATCATTAATAA
CACTGTTTACACAAAAGTTG ATG GTGTTGATGTAGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAG
CATTTG AG
CTTTG G G CTA AG CG CAACATTAAAC CAGTACCAG AGGTGAAAATACTCAATAATTTG G GTGTG
GACATTGCTGCTAATACT
GT G ATCTG G G A CTA CAAAAG AG AT G CTC C AG CA CATATATCTACTATTG GT G
TTTGTTCTAT G ACT G ACATAG CC AAG AAA
CCAACTG AAACG ATTTGTG CAC CA CTCA CTGT CTTTTTT G ATG GTAG AGTTGATG GTCAAGTAG
ACTTATTTAG AAATG CCC
GTAATG GTGTTCTTATTACAGAAG G TAG TGTTAAAG GTTTACAACCATCTGTAG GTCCCAAACAAG
CTAGTCTTAATG GAG
TCACATTAATTG G AG AAG CCGTAAAAACACAGTTCAATTATTATAAGAAAGTTG ATG G
TGTTGTCCAACAATTACCTG AAA
CTTACTTTA CT CAG A G TAGAAATTTACAAG AATTTAAACCCAGG AGTCAAATGGAAATTG
ATTTCTTAGAATTAG CTATG GA
TG AATTCATTG AA CG G TATA AATTA G AA G G CTATG CCTTCG AA CATATCGTTTATG G AG
ATTTTAGTCATAGTCAGTTAGGT
G GTTTACATCTACTG ATTG GACTAG CTAAACGTTTTAAG G AATCACCTTTTGAATTAGAAGATTTTATTC
CTATGG AC AGTA
CAG TTAAAAACTATTT CATAA CAG AT G CG CAAACAG GTTCATCTAAGTGTGTGTGTTCTG TTATT G
ATTTATTACTTG AT G A
TTTTGTTGAAATAATAAAATC CCAAG ATTTATCTGTAGTTTCTAAG G TTG TCAAAG TG A CTATT G
ACTATACA G AAATTTCAT
TTATG CTTTG GTGTAAAG ATG G CCATG TAG AAACATTTTAC CCAAAATTACAATCTAGTCAAG CGTG
GC AAC CG GGTGTTG

CTATG CCTAATCTTTACAAAATG CAAAGAATG CTATTAG AAAAGTGTG ACCTTCAAAATTATG GTG
ATAGTG CAACATTACC
TAAAGG CATAATGATG AATGTCG CAAAATATACTCAACTG TGTCAATATTTAAACACATTAACATTAG
CTGTACCCTATAAT
ATG AG AG TTATA CATTTTG GTG CT G GTTCTGATAAAG G AG TT G CAC C AG GTACAG
CTGTTTTAAG ACAGTG GTTG CCTACG
G GTACG CTG CTTGTCGATTCAG ATCTTAATG ACTTTGTCTCTG ATG CAGATTCAACTTTG ATTG GTG
ATTGTG CAACTGTAC
ATACAG CTAATAAATG G G ATCTCATTATTAG T G ATATG TA C G ACC CTAAG ACTAAAAATG
TTACAAAAG AAAATG A CTCTA
AAG AG G GTTTTTTCACTTACATTTGTG G GTTTATACAACAAAAG CTAG CTCTTG G AG GTTCCGTG G
CTATAAAGATAACAG
AACATTCTTGG AATG CTGATCTTTATAAG CTCATG G G AC ACTTC G CATG GT G GAC AG CCTTTG
TTACTAATGTGAATG CGTC
ATC ATCTG AA G CATTTTTAATTG G ATGTAATTATCTTG G CAAACCAC G CG AACAAATAG AT G G
TTATG TCATG CATG CAAAT
TACATATTTTG GAG G AATA C AAATCC AATTC AG TT G TCTTCCTATTCTTTATTT G ACATG AG
TAAATTT CCCCTTAAATTAAG
G G GTACTG CTGTTATGTCTTTAAAAG AAGGTCAAATCAATGATATG ATTTTATCTCTTCTTAGTAAAG G
TAG ACTTATAATT
AG A G AAAACAACAG AG TTG TTATTT CTAG TG AT G TT CTTG TTAACAACTAAACG
AACAATGTTTGTTTTTCTTGTTTTATTG C
CACTAGTCTCTATTCAGTGTGTTAATCTTACAACCAG AACTCAATTACCCCCTG
CATACACTAATTCTTTCACACGTG GTG TT
TATTACCCTG A CAAAG TTTT CAG ATCCT CAG TTTTACATTC AACTC AG G A CTTG TTCTTACCTTT
CTTTTCCAATG TTACTT G G
TT CCATG CTATACATGTCTCTG G G AC C AATG GTACTAAG AG
GTTTGATAACCCTGTCCTACCATTTAATGATG GTGTTTATTT
TG CTTCCACTG AG AA G TCTAACATAATAAG AG G CTG G ATTTTTG GTACTACTTTAGATTCG AAG A
C CCA G TCCCTACTTATT
G TTAATA AC G CTACTAATG TT G TT ATTAAAGTCT G TG AATTT CAATTTTG TAATG
ATCCATTTTTG G GTGTTTATTACCACAA
AAAC AACAAAA G TT G TAT G GAAAGTG AG TTCAG AG TTTATTCTA GTG CGAATAATTG
CACTTTTGAATATGTCTCTCAG C CT
TTTCTTATG G ACCTTGAAG GAAAACAG G GTAATTTCAAAAATCTTAG G G
AATTTGTGTTTAAGAATATTGATG GTTATTTTA
AAATATATTCTAAG CACACG CCTATTAATTTAGTG C GT G ATCT CCCT CAG G GTTTTTCG G
CTTTAGAACCATTG G TAG ATTT
G CCAATAG GTATTAACATCACTAG GTTTCAAACTTTACTTG CTTTACATAGAAGTTATTTG ACT CCTG
GTGATTCTTCTTCAG
GTTG GACAG CTG GT G CTG CAG CTTATTATGTG G GTTATCTTCAACCTAG G
ACTTTTCTATTAAAATATAATGAAAATG GAAC
CATTACAG AT G CT G TA G ACT G T G CACTT G ACCCTCT CTCAG AAAC AAAG TG TAC G TT
G AAATC CTTC ACTG TAG AAAAAG G
AAT CTAT CAAACTTCTAACTTTAG A G TC CAACCAACAG AATCTATTG TTAG
ATTTCCTAATATTACAAACTTGTG CC CTTTTG
GTGAAGTTTTTAACG C CAC CAG ATTTG CATCTGTTTATG CTTG GAACAG G AAG AG AATC AG
CAACTG TGTTGCTGATTATTC
TGTCCTATATAATTC CG CAT CATTTTCC ACTTTTAAG TG TTATG G AG TG TCTCCTACTAAATTAAATG
ATCTCTG CTTTACTAA
TGTCTATG CAG ATTC ATTT G TAATTAG AG GTGATG AAGTC AG A CAAATC G CTCC AG GG
CAAACTG G AAAGATTG CTGATTA
TAATTATAAATTACCAG ATGATTTTACAG G CTG CGTTATAG CTTG GAATTCTAACAATCTTG ATTCTAAG
GTTG GIG GTAAT
TATAATTACCG GTATAGATTGTTTAG G AAG TCTAATCTCAAAC CTTTTG AG AG AG
ATATTTCAACTGAAATCTATCAG G CCG
G TAG CACACCTTG TAATG GTGTTG AAG GTTTTAATTGTTACTTTCCTTTACAATCATATG G
TTTCCAACCCACTAATG G TG TT
G G TTAC CAACC ATACAG AG TAG TAG TACTTTCTTTT G AACTTCTACATG C ACC AG CAA
CTGTTTG TG G A CCTAAAAA G T CTA
CTAATTTG GTTAAAAACAAATGTGTCAATTTCAACTTCAATG GTTTAACAG GCACAG GTG TTCTTACTG AG
TCTAACAAAAA
GTTTCTGCCTTTCCAACAATTTG G CAG AG ACATTG CTGACACTACTGATG CTG TCC G TG ATC CACAG
ACACTTG AG ATT CTT
G ACATTACACCATGTTCTTTTG GTG GTGTCAGTGTTATAACACCAG G AACAAAT ACTT CTAACCAG GTTG
CTGTTCTTTATC
AG G GTGTTAACTG CACAG AAGTC CCTGTTG CTATTCATG CAGATCAACTTACTCCTACTTG G
CGTGTTTATTCTACAG GTTC
TAAT G TTTTT CAAAC AC G TG CAG G CTGTTTAATAG G G G CT G AA CATG TC
AACAACTCATATG AG TG T G ACATACCCATTG G
TG CAGGTATATG CG CTAGTTATCAG ACT CAG ACT AATTCTCCTCG GCGGG CACGTAG TG TAG
CTAGTCAATCCATCATTG C
CTA C ACTATG TC ACTT G GTG CAG AAAATT CAG TT G CTTACTCTAATAACTCTATTG
CCATACCCACAAATTTTACTATTAGTG
TTACCACAGAAATTCTACCAGTGTCTATG ACCAAG ACATC AG TAG ATT GTACAATGTACATTTGTG
GTGATTCAACTG AATG
CAG CAATCTTTTGTTGCAATATG G CAGTTTTTGTACACAATTAAACC GTG CTTTAACTG GAATAG CTGTTG
AACAAG ACAAA
AACACCCAAGAAGTTTTTG CA CAAG TCAAAC AAATTTACAAAA CACCA CCAATT AAAG ATTTTG GT G
GTTTTAATTTTTCAC
AAATATTACCAGATCCATCAAAACCAAG CAAG AG GTCATTTATTG AAG AT CTACTTTT CAACAAAG TG
ACACTTG CAG AT G
CTG G CTT CAT CAAAC AATATG GTGATTG CCTTG GTGATATTG CTG CTAG AG ACCTCATTTG TG
CACAAAAGTTTAACG G CCT
TACTGTTTTG CCACCTTTG CTCACAGATGAAATGATTG CTCAATACACTTCTG CA CTG TTAG CG G
GTACAATCACTTCTG G TT
G GACCTTTG GTG CAG GTG CTG CATTACAAATACCATTTG CTATG CAAATG G CTTATAG GTTTAATG
GTATTG G AG TTACAC
AG AATG TTCT CTATG AG AACCAAAAATTG ATTG C CAA CC AATTTAATA G T G CTATTG G
CAAAATTCAAG ACTCACTTTCTTC
CAC AG CAA G TG C ACTT G G AA AACTT CAAG ATG TG GTCAACCAAAATG CACAAG CTTTAAACA
C G CTTG TT AAACAACTTA G
CTCCAATTTTG GIG CAATTTCAAG TGTTTTAAATG ATATCCTTTCACGTCTTGACAAAGTTG AG G
CTGAAGTG CAAATTG AT
AG G TTG ATCACAG G C AG ACTTCAAAGTTTG CA G ACATATG T G ACTCAACAATTAATTAG AG
CTG CAG AAATCA G AG CTTCT
G CTAATCTTG CTG CTACTAAAATG T CAG AG TG TG TACTT G G ACAATCAAAAAG AG TTG
ATTTTTGTG GAAAGG G CTATCAT
CTTATGTCCTTCCCTCAGTCAG CA CCTC ATG G TG TA G TCTTCTT G C AT G TG ACTTATGTCCCTG
CACAAGAAAAG AACTTCAC
AA CTG CT CCTG CCATTTG TCATG ATG G AAAA G CA CA CTIT CCTC G TG AA G G TGICTIT
GUT CAAATG G CA CA C A CTG GTTT
GTAACACAAAG G AATTTTTATG AAC CAC AAATCATTACTAC AG AC AACACATTTG TG T CTG
GTAACTGTG ATGTTGTAATAG
GAATTGTCAACAACACAGTTTATGATCCTTTG C AAC CT G AATTAG ACTCATTCAAG GAG G AG TTAG
ATAAATATTTTAAG AA
TCATACATCACCAGATGTTGATTTAG GTG ACATCTCTG G CATTAATG CTTCAGTTGTAAACATTCAAAAAG
AAATTG AC C G C
CTCAATG AG GTTG CC AAG AATTTAAATG AATCTCTCATC GATCTCCAAG AACTTG G AAAG TATG AG
CAGTATATAAAATG G

CCATG GTACATTTG G CTAG GTTTTATAG CT G G CTTG ATTG CC ATAG TAATG GTG ACAATTATG
CTTTG CTG TATG AC CAG TT
G CTG TAG TTG TCTC AAG G G CTGTTGTTCTTGTG GATCCTG CT G CAAATTTG ATG AA G ACG
ACTCTG AG CCAGTG CTCAAAG
G AG T CAAATTACATTA CAC ATAAAC G AACTTATG G ATTTG TTTAT G AG AATCTTCACAATTG G
AACTGTAACTTTGAAG CAA
G GTGAAATCAAG GATG CTACTCCTTCAGATTTTGTTCG CG CTACTG CAACG ATACCGATACAAG
CCTCACTCCCTTTCGG AT
G G CTTATTGTTG G CGTTG CACTTCTTG CTGTTTTTCATAG CG CTTC CAAAAT CATAAC CCT
CAAAAA G AG ATG G CAACTAG C
ACT CTC CAAG GGTGTT CA CTTTG TTTG CAACTTG CTG TTGTTGTTTGTAAC AG TTTACTC
ACACCTTTTG CTCG TTG CTG CTG
G CCTTG AAG CCCCTTTTCTCTATCTTTATG CTTTAGTCTACTTCTTG C AG AG TATAAA CTTT G TAA
G AATAATAATG AG G CTT
TG G CTTTG CTG G AAATG CC G TT CCAAAAACC CATTACTTTATGATG CC AACTATTTT CTTT G
CT G GCATACTAATTGTTAC GA
CTATTG TATAC CTTA CAATAG TG TAACTT CTTCAATTG TC ATTACTTC AG G T G ATG G
CACAACAAGTCCTATTTCTGAACATG
ACTACCAG ATTG GTG GTTATACTG AAAAATG G G AATCTGG AG TAAAAG ACT GTG TTGTATTAC
ACAG TTACTTCACTTCAG
ACTATTACCAG CTG TA CTCAACTCAATTG AG TA CAG ACACTG GTGTTG
AACATGTTACCTTCTTCATCTACAATAAAATTGTT
G ATG AG CCTG AAGAACATGTCCAAATTCACACAATCGACG G TT CATCC G G AG TTG TTAATC C AG
TAATG G AACCAATTTAT
G AT G AAC C G AC G AC G ACTAC TAG CGTG CCTTTGTAAG CAC AAG CT G ATG AG TAC G
AA CTTATG TA CTCATTC G TTTC G G AA
GAG ACAG G TA C GTT AATAG TTAATAG CGTACTTCTTTTTCTTGCTTTCGTG
GTATTCTTGCTAGTTACACTAG CC ATCCTTAC
TG CG CTTCGATTGTGTG C G TA CTG CTG CAATATTGTTAACGTG AG TCTTG TAAAA CCTT
CTTTTTAC G TTTACT CTCG TGTTA
AAAATCTG AATTCTTCTAG AG TTC CTG AT CTTCTG GTCTAAACG AA CTAAATATTATATTA G
TTTTTCTG TTTG G AACTTTAAT
TTTAG CCATG G TA G ATTCCAACG G TACTATTA CC G TTG AA G AG CTTAAAAAG CT CCTT G
AACAATG G AACCTAGTAATAG G
TTTCCTATTCCTTACATG GATTTGTCTTCTACAATTTG CCTATG CCAACAG G AATAG
GTTTTTGTATATAATTAAGTTAATTTT
TCTCTG G CTGTTATG G CCAGTAACTTTAG CTTGTTTTG TG CTTG CTG CTGTTTACAG AATAAATTG G
ATCACCG GTG G AATT
G CTATCG CAATG G CTTGTCTTG TAG G CTTGATGTGG CTCAG CTACTTCATTG
CTTCTTTCAGACTGTTTG CG CGTACG CG TT
CCATGTG GTC ATTC AATCCAG AAA CTAAC ATTCTTCT CAAC G TG CC ACTC CATG G C
ACTATTCT G ACC AG AC C G CTTCTA G A
AAGTGAACTCGTAATCG GAG CTGTGATCCTTCGTG G ACAT CTTC G TATTG CT G G A CACCAT CTAG
G AC G CTGTGACATCAA
G GACCTG CCTAAAGAAATCACTGTTG CTACATCACGAACG CTTTCTTATTACAAATTGG GAGCTTCG CAG
CGTGTAG CAG G
TG ACTCAGGTTTTG CTG CATACAGTCG CTAC AG GATTGG CAACTATAAATTAAAC ACAG A CCATT C
CAG TAG CAGTG ACAA
TATTG CTTTG CTTG TACA G TAAG T G AC AACAG ATGTTTCATCTC GTTG ACTTTCAG G TTA
CTATA G C AG AG ATATTACTAATT
ATTATG A GG ACTTTTAAAG TTTCCATTTG
GAATCTTGATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAAC
TG AG AATAAATATTCT CAATTAG AT G AAG AG CAA CCAAT G GAG ATTG ATTAAAC G A ACATG
AAAATTATT CTTTTCTTG GC
ACT G ATAACACT C G CTACTTGTG AG CTTTATCACTACCAAG AG TG TGTTAG AG G TACAAC AG
TACTTTTAAAAG AACCTTG C
TCTTCTGGAACATACG AG G G CAATTCAC CATTT CAT CCTCTAG CTGATAACAAATTTGCACTGACTTG
CTTTAG CA CT CAATT
TG CTTTTG CTTGTCCTG AC G G CGTAAAACACGTCTATCAGTTACGTG CCAG ATCAG TTT CAC
CTAAACT GTTC ATCAG ACAA
GAG G AAGTTCAAG AACTTTACTCTCCAATTTTTCTTATTGTTG CG G CAATAGTGTTTATAACACTTTG
CTTC AC ACTC AAAAG
AAAG A CAG AATG ATTG AACTTTCATTAATT G ACTT CTATTTG TG CTTTTTAG CCTTTCTG
CTATTCCTTGTTTTAATTATGCTT
ATTATCTTTTG G TT CTCACTTG AACTG CAAG ATCATAATG AAACTT G TC AC G
CCTAAACGAACATGAAATTTCTTGTTTTCTT
AG G AAT CAT CACAACT G TAG CTG C ATTT CACCAAG AATG TAG TTTACAG TCATG TACT
CAACAT CAACCATATG TAG TT G AT
G AC CCG T GTCCTATT CACTT CTATT CTAAATG G TATATTAG AG TAG G AG CTAG AAAAT CAG
C A CCTTTAATT G AATTG TG CG
TG GATG AG G CT G G TTCTAAATC ACCCATTCAG TA CAT CG ATATC G
GTAATTATACAGTTTCCTGTTTACCTTTTACAATTAAT
TG CCAG GAACCTAAATTG G GTAGTCTTGTAGTG CGTTG TT CGTT CTATG AAG ACTTTTTAG AG
TATC ATG AC GTTC GTG TTG
TTTTAG ATTTCATCTAAACG AACAAACTATAATGTCTG ATAATG GACCCCAAAATCAG CG AAATG
CACCCCG CATTACGTTT
G GTG G ACC CTCAG ATTCAACTG G CAGTAACCAGAATG GAGAACG CAGTG G G G CG
CGATCAAAACAACGTC G G CC CCAAG
GTTTACCCAATAATACTG CGTCTTG GTTCACCG CTCTCACTCAACATG G CAAG GAAG ACCTTAAATT C
CCTC G AG G ACAAG
G CGTTCCAATTAACACCAATAG C AG TC CAG ATG ACCA AATTG G CTACTACCGAAG AG CTAC CAG
AC G AATT C G TG GTG GT
G AC G GTAAAATG AAAG AT CTCAG TCCAAG ATG GTATTTCTACTACCTAG GAACTG G G CCAGAAG
CTG G A CTTCC CTATG GT
G CTAACAAAGACG G CATCATATG G GTTG CAAC TG AG GG AG CCTTG AATAC ACCAAAAG AT
CACATTG G CACCCGCAATCC
TG CTAACAATG CT G CAATCGTG CTACAACTTCCTCAAG GAACAACATTG CC AAAAG G CTTCTAC G C
AG AAG G GAG CAG A G
G CG G CAGTCAAGCCTCTTCTCGTTCCTCATCACGTAGTCG CAACAGTTCAAGAAATTCAACTCCAG G CAG
CAG TAG G G G AA
TTTCTC CTG CTAGAATG G CTG G CAATG G CG GTG ATG CTG CT CTTG CTTTG CT G CTG
CTTGACAG ATTG AACC AG CTTG A G A
G CAAAATGTCTG GTAAAG G CCAACAACAACAAG G CCAAACTGTCACTAAGAAATCTG CT G CT G AG G
CTTCTAAG AAG CCT
CG G CAAAA ACG TA CTG CCACTAAAG CATACAATGTAACACAAG CTTTCG G CAG
ACGTGGTCCAGAACAAACCCAAG G
AAATTTTG G G GACCAG G AA CTAAT CAG AC AAG G AACTG ATTACAAACATTG G CCG CAAATTG
CAC AATTTG CCCCCAG CG
CTTCAG C GTTCTTCG GAATGTCG CG CATTG G CATG GAAGTCACACCTTCGG G AACGTG GTTG AC
CTA CA CAG GTG CCATCA
AATTG G ATG A C AAA G AT CCAAATTTCAAA G ATCAA G TCATTTTG CTG A ATAA G CATATTG
A C G CATA CAAAA C ATTT CCA CC
AACA G AG CCTAAAAAG G ACAAAAAG AA G AAG G CTG AT G AAA CT CAA G CCTTACCG C AG
AG A CAG AAG AAAC AG CAAACT
GTGACTCTTCTTCCTG CTG C A G ATTTG GATGATTTCTCCAAACAATTG CAACAATCCATG AG CAG TG
CT G A CTC AACTC AG G
CCTAAACTCATG CAG AC CA CACAAG G CAGATG G G CTATATAAACGTTTTCG CTTTTC CGTTTACG
ATATATAGTCTACTCTT
GTG CAG AATGAATTCTCGTAACTACATAG CACAAG TAG ATG TAG TTAACTTTAATCT CACATAG
CAATCTTTAATCAGTGTG

TAACATTAG G GAG G ACTTG AAAG AG CCACCACATTTTCACCGAG G CCACG CG
GAGTACGATCGAGTGTACAGTG AACAAT
G CTAGG GAGAG CTG CCTATATG GAAG AGCCCTAATGTGTAAAATTAATTTTAGTAGTG CTATCC
SEQ ID NO: 25 >QQV21856.1: S surface protein M FVF LVL LP LVSI QCVN LTTRTQLPPAYTNSFTRGVYYPDKVF RSSVLHSTQDLFLPFFSNVTWF HAI
HVSGTNGTKR F D N PVLP F

N KSCM ES E F RVYSSAN NCTF EYVS
QPFLMDLEGKQGNFKNLREFVFKNIDGYFKIYSKHTPINLVRDLPQGFSALEPLVDLPIGINITRFQTLLALHRSYLTP
GDSSSGWT
AGAAAYYVGYLQPRTFLLKYN E NGTITDAVDCALDP LSETKCTL KSFTV EKG IYQTSNF
RVQPTESIVRFPN ITN LCPFG EV F NATR
FASVYAWN RKR ISNCVADYSVLYNSASFSTF KCYGVSPTKLN DLCFINVYADSFVIRG DEVRQIAPGQTG
KIADYNYKLPDDFTG
CVIAWNSN N LDSKVGG NYNYRYRLFRKSN LKPFE RDISTEIYQAGSTPCNGVEG FNCYFPLQSYG
FQPTNGVGYQPYRVVVLSF
E LLHAPATVCG PKKSTN LVKNKCVN FNFNG LTGTGVLTESNKKFLPFQQFG R DIADTTDAVR DPQTLE I
LD ITPCSFG GVSVITPG
TNTS NQVAVLYQGVNCTEVPVAI HADQLTPTWRVYSTGSNVFQTRAGCLI GAEHVN NSYECD IP IGAG
ICASYQTQTNSP RRAR
SVASQSI IAYTMSLGAENSVAYSN NSI Al PIN FTISVTTE I LPVS MTKTSVDCT MYICG DSTECSN
LLLQYGSFCTQLN RALTG IAVE
QD KNTQEV FAQVKQIYKTP PI KD FG G FN FSQI LP DPSKPSKRSF I E DL LF NKVTLADAG Fl KQYG DC LGD IAARDLICAQKFNG LTV
LP P LLTDE M IAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRF NG IGVTQNVLYENQKLIANQFNSAIG
KIQDSLSSTASAL

RAAE I RASANLAATKMSE
CVLG QSKRVDFCG KGYHLMSFPQSAPHGVVF LHVTYVPAQEKN FTTAPAICH DG KAH FP
REGVFVSNGTHWFVTQRN FYE PQ
IITTDNTFVSGNCDVVIGIVNNTVYDPLQP ELDSF KEELDKYFKN HTSPDVDLG
DISGINASVVNIQKEIDRLNEVAKNLNESLIDL

DDSEPVLKGVKLHYT
SEQ ID NO: 26 >M W306426.1 Severe acute respiratory syndrome coronavirus 2 isolate SARS-CoV-2/hu nna n /USA/CA-CZB-12872/2020, complete genome. [Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)]. Californian B.1.429 lineage ACTTTCGATCTCTTGTAGATCTGTTCTCTAAACGAACTTTAAAATCTGTGTG GCTGTCACTCGG CTG
CATGCTTAGTGCACTC
ACGCAGTATAATTAATAACTAATTACTGTCGTTGACAGGACACGAGTAACTCGTCTATCTTCTGCAGGCTGCTTACGGT
TTC
GTCCGTGTTG CAGCCGATCATCAGCACATCTAGGTTTTGTCCGGGTGTGACCGAAAGGTAAGATG
GAGAGCCTTGTCCCT
GGTTTCAACGAGAAAACACACGTCCAACTCAGTTTGCCTGTTTTACAG
GTTCGCGACGTGCTCGTACGTGGCTTTGGAGAC
TCCGTG GAG GAGGTCTTATCAGAG G CACGTCAACATCTTAAAGATG G CACTTGTG G
CTTAGTAGAAGTTGAAAAAG G CGT
TTTGCCTCAACTTGAACAGCCCTATGTGTTCATCAAACGTTCGGATGCTCGAACTGCACCTCATGGTCATGTTATGGTT
GAG
CTGGTAGCAGAACTCGAAGGCATTCAGTACGGTCGTAGTGGTGAGACACTTGGTGTCCTTGTCCCTCATGTGGGCGAAA
T
ACCAGTG G CTTACCG CAAG GTTCTTCTTCGTAAG AACGGTAATAAAG GAG CTG GTG G CCATAGTTACG
GCG CCGATCTAA
AGTCATTTGACTTAGG
CGACGAGCTTGGCACTGATCCTTATGAAGATTTTCAAGAAAACTGGAACACTAAACATAGCAGTG
GTGTTACCCGTGAACTCATGCGTGAGCTTAACGGAGGGGCATACACTCGCTATGTCGATAACAACTTCTGTGG
CCCTGATG
G CTACCCTCTTGAGTG CATTAAAGACCTTCTAG CAC GTG CTG GTAAAG CTTCATG
CACTTTGTCCGAACAACTG GACTTTAT
TG ACACTAAGAG G G GTGTATACTG CTG CCGTG AACATG AG CATGAAATTG CTTG GTACACG G
AACGTTCTGAAAAG AG CT
ATGAATTGCAGACACCTTTTGAAATTAAATTGGCAAAGAAATTTGACATCTTCAATG
GGGAATGTCCAAATTTTGTATTTCC
CTTAAATTCCATAATCAAGACTATTCAACCAAGGGTTGAAAAGAAAAAGCTTGATGGCTTTATGGGTAGAATTCGATCT
GT
CTATCCAGTTGCGTCACCAAATGAATGCAACCAAATGTGCCTTTCAACTCTCATGAAGTGTGATCATTGTGGTGAAACT
TCA
TGGCAGACGGGCGATTTTGTTAAAGCCACTTGCGAATTTTGTGGCACTGAGAATTTGACTAAAGAAGGTGCCACTACTT
GT
GGTTACTTACCCCAAAATGCTGTTGTTAAAATTTATTGTCCAGCATGTCACAATTCAGAAGTAGGACCTGAGCATAGTC
TTG
CCG AATACCATAATGAATCTG G CTTGAAAACCATTCTTCGTAAG G GTG G TCG CACTATTG CCTTTG
GAG GCTGTGTGTTCTC
TTATGTTGGTTGCCATAACAAGTGTGCCTATTGGGTTCCACGTGCTAGCGCTAACATAGGTTGTAACCATACAGGTGTT
GTT
GGAGAAGGTTCCGAAGGTCTTAATGACAACCTTCTTGAAATACTCCAAAAAGAGAAAGTCAACATCAATATTGTTGGTG
AC
TTTAAACTTAATGAAGAGATCGCCATTATTTTGGCATCTTTTTCTGCTTCCACAAGTGCTTTTGTGGAAACTGTGAAAG
GTTT
GGATTATAAAGCATTCAAACAAATTGTTGAATCCTGTGGTAATTTTAAAGTTACAAAAGGAAAAGCTAAAAAAGGTGCC
TG
GAATATTGGTGAACAGAAATCAATACTG AGTCCTCTTTATGCATTTG CATCAG AG G CTG CTCGTGTTGTACG
ATCAATTTTC
TCCCGCACTCTTGAAACTGCTCAAAATTCTGTGCGTGTTTTACAGAAGGCCGCTATAACAATACTAGATGGAATTTCAC
AGT
ATTCACTG AG ACTCATTGATG CTATGATGTTCACATCTG ATTTG G CTACTAACAATCTAGTTGTAATG G
CCTACATTACAG G
TGGTGTTGTTCAGTTGACTTCGCAGTGGCTAACTAACATCTTTGGCACTGTTTATGAAAAACTCAAACCCGTCCTTGAT
TGG
CTTGAAGAGAAGTTTAAGGAAGGTGTAGAGTTTCTTAGAGACGGTTGGGAAATTGTTAAATTTATCTCAACCTGTGCTT
GT
GAAATTGTCGGTGGACAAATTGTCACCTGTGCAAAGGAAATTAAGGAGAGTGTTCAGACATTCTTTAAGCTTGTAAATA
AA
TTTTTG GCTTTGTGTG CTGACTCTATCATTATTG GTG GAG CTAAACTTAAAG CCTTG AATTTAG
GTGAAACATTTGTTACG C
ACTCAAAGGGATTGTACAGAAAGTGTGTTAAATCCAGAGAAGAAACTGGCCTACTCATGCCTCTAAAAGCCCCAAAAGA
A

ATTATCTT CTTA G AG G GAG AAACACTTCCCAC AG AAG TGTTAACAG AG GAAGTTGTCTTGAAAACTG
GTGATTTACAACCA
TTAG AACAACCTACTAGTG AAG CTG TTG AAG CT C CACTG GTTG G TA CACC AG TTTG TATTAAC
G G G CTTATGTTG CTC G AA
ATC AAAG A CACAG AAAAG TACT G TG CCCTTG CAC CTAATATG ATG
GTAACAAACAATACCTTCACACTCAAAG G CG GTG CA
CCAACAAAG GTTACTTTTG G TG AT G ACACTGTG ATAG AAGTG CAAG G TTA CAAG AG TGT
GAATATCACTTTTG AACTTG AT
GAAAG G ATTG ATAAAG TACTTAATG AG AAG T G CTCTG CCTATACAGTTG AACTCG G TA CAG
AAG TAAAT G AG TT C G C CTGT
GTTGTG G CAG ATG CTGTCATAAAAACTTTG CAAC CAGTATCTG AATTACTTACACCACTG G G
CATTGATTTAGATGAGTG G
AG TATG G CTACATACTACTTATTTGATGAGTCTG GTG AG TTTAAATTG G CTTCACATAT GTATTG TT
CTTTTTACC CTCCAG A
TG AG G AT G AAG AAGAAG GTG ATTG TGAAG AA G AA G AG TTTG AG CCAT CAACT CAATAT
G AG TATG G TACT G AAG ATG AT
TACCAAG GTAAACCTTTG G AATTTG GTG CCACTTCTG CTG CTCTT CAACCTG AAG AAG AG CAAG
AAGAAGATTG GTTAG AT
GATGATAGTCAACAAACTGTTG GTCAACAAG ACG G CAG TG AG G AC AATCAG ACAACTACTATTCAAA
CAATTG TTG AG GT
TCAACCTC AATTAG AG ATG G AACTTACACCAG TTG TTCA G ACTATTG A AGTG AATAGTTTTAGTG
GTTATTTAAAACTTACT
G AC AATG TATAC ATTAAAAATG CAG A CATTG TG G AAG AA G CTAAAAAG G TAAAA CCAAC A
G TG G TT GTTAATG CAG CCAA
TGTTTACCTTAAACATG GAG GAG GTGTTG C AG GAG CCTTAAATAAG G CTACTAACAATG CCATG
CAAGTTGAATCTG ATG A
TTACATAG CTACTAATG GACCACTTAAAGTG GGTG G TAG TTG T G TTTTAAG CG G ACACAATCTTG
CTAAACACTG TCTTCAT
GTTGTCG GCCCAAATGTTAACAAAG GTG AAG ACATTC AACTT CTTAAG AG TG CTTATG
AAAATTTTAATCAG CAC G AAG TT
CTACTTG CACC ATTATTATC AG CT G GTATTTTTG GTG CTG A C CCTATACATTCTTTAAG AG TTTG
TG TA G AT ACTG TTC G CAC
AAATGTCTACTTAG CTGTCTTTGATAAAAATCTCTATG AC AAACTTGTTTCAAG CTTTTTG
GAAATGAAGAGTGAAAAG CAA
GTTGAACAAAAG ATCG CTG AG ATTC CTAAAG AG G AAGTTAAG CCATTTATAA CTG AAAG
TAAACCTTCAG TTG AA CAG AG
AAAA CAAG AT G ATA AG AAAATCAAA G CTTGTGTTG AAGAAGTTACAACAACTCTGG AAG AAACTAA
G TTC CTCA CA G AAA
ACTTGTTACTTTATATTGACATTAATG G CAATCTTCATCC AG ATT CTG CCACTCTTG TTAG TG A CATT
G ACAT CACTTTCTTAA
AG AAAG AT G CTCCATATATAGTG G GTGATGTTGTTCAAGAG G GTGTTTTAACTG CTGTG
GTTATACCTACTAAAAAG G CTG
GTG G CA CTACTG AAATG CTAG CGAAAG CTTTG AG AAAAGTG CCAACAG
ACAATTATATAACCACTTACCCG G GTCAG G GT
TTAAATG G TTA CA CTG TAG A G GAG G CAAAGACAGTG CTTAAAAAGTGTAAAAGTG CCTTTTA
CATTCTAC CAT CTATTATCT
CTAATG AG AAG C AA G AAATT CTTG G AACTGTTTCTTG GAATTTGCG AG AAATG CTTG CA CATG
CAGAAG AAACACG CAAA
TTAATG C CTGTCTGTGTG G AAA CTAAAG CCATAG TTTCAACTATACAG CGTAAATATAAG G G
TATTAAAATA C AAG AG G GT
GTG GTTGATTATG GTG CTAG ATTTTACTTTTACACCAGTAAAACAACTGTAG CGTCACTTAT CAA
CACACTTAACGAT CTAA
ATG AAACTCTTGTTACAATG CCACTTG G CTATGTAACACATG G CTTAAATTTG G AAG AAG CTG CTC
G GTATATG AG AT CTCT
CAAAGTG CCAG CTACAGTTTCTGTTTCTTCACCTG ATG CTGTTACAG CGTATAATG
GTTATCTTACTTCTTCTTCTAAAACAC
CTGAAG AACATTTTATTGAAACCATCTCACTTG CTG GTTCCTATAAAGATTG GTCCTATTCTG
GACAATCTACACAACTAG G
TATA G AATTTCTTAAG AG AG G TG ATAAAAG TG TATATTACACTAG TAATCCTAC CAC
ATTCCACCTAG ATG GTGAAGTTATC
ACCTTTGACAATCTTAAGACACTTCTTTCTTTG AG AG AAGTG AG G ACTATTAAG G TG TTTAC AACAG
TAG AC AACATTAACC
TC CA CAC G CAAGTTGTG G ACATGTCAATG AC ATATG GACAACAGTTTGGTCCAACTTATTTG GATG
GAG CTGATGTTACTA
AAATAAAACCTCATAATTCACATGAAG G TAA AACATTTTATG TTTTAC CTAATG AT G AC ACTCTA C G
TG TTG AG G CTTTTG A
GTACTAC CAC ACA ACTG ATCCTAGTTTTCTG G G TAG GTACATGTCAG CATTAAATCACACTAAAAAGTG
G AAATACCCACA
AG TTAAT G G TTTA ACTT CTATTAAAT G G G CAGATAACAACTGTTATCTTG CCACTG CATTG
TTAACACTC CAACAAATAG AG
TT G AAG TTTAATCCACCTG CT CTA CAAG ATG CTTATTACAG A G CAAG G G CTG GTGAAG CTG
CTAACTTTTGTG C A CTTATCT
TAG CCTACTGTAATAAG AC AG TAG G TG AG TTAG GTG AT G TTAG A G AAACAATG AG
TTACTTG TTTCAACATG CCAATTTAG
ATTCTTGCAAAAG AG T CTT G AA C G TG G TG T G TAAAACTT G TG G AC AACAG CAG AC
AACCCTTAAG G GT G TA G AAG CT G TT
ATGTACATG G G CACACTTTCTTATGAACAATTTAAG AAAG GTGTTCAGATACCTTGTACGTGTG
GTAAACAAG CTACAAAA
TAT CTAG TACAA CAG G A G TCA CCTTTTG TTATG ATGTCAG C A CCACCTG CT CAG TATG AA
CTTAAG CAT G G TA CATTTACTT
GTG CTAGTG AG TA CACTG GTAATTACCAGTGTG
GTCACTATAAACATATAACTTCTAAAGAAACTTTGTATTG CATAG ACG
GTG CTTTACTTACAAAG T CCT C AG AATACAAAG GTCCTATTACG G ATG TTTT CTACAAA G AAAAC
AG TTACACAAC AACCAT
AAAACCAGTTACTTATAAATTG GATG G TG TTG TTTG TAC A G AAATTG AC CCTAA G TTG G
ACAATTATTATAAG AAA G ACAA
TT CTTATTTCACAG AG CAACCAATTGATCTTGTACCAAACCAACCATATCCAAACG CAAG CTTC G
ATAATTTTAAG TTTG TA
TG TG ATAATAT CAAATTTG CTG AT G ATTTAAAC CAGTTAACTGGTTATAAGAAACCTG CTTC AAG AG
AG CTTAAAGTTACAT
TTTTCCCTG ACTTAAATG GTG ATG TG G TG G CTATTG ATTATAAACACTACACACCCTCTTTTAAG
AAAG GAG CTAAATTG TT
ACATAAACCTATTGTTTG GCATGTTAACAATG CAACTAATAAAG CCACGTATAAACCAAATACCTG
GTGTATACGTTGTCTT
TG GAG C ACAAAA CC AG TTG AAACATC AAATT C G TTTG AT G TA CTG AA GTCAG AG G AC
G C G CAG G GAATG G ATAATCTTG C
CT G CGAAGATCTAAAACCAGTCTCTGAAG AAG TAG TG G AAAATCCTA CCATACAG A AAG AC G TT
CTTG AGTGTAATGTG A
AAACTACCG AAG TTG TAG G AG ACATTATACTTAAAC CAG CAAATAATAG TTTAAAAATTAC AG AAG
AG GTTG G CCACACA
G AT CTAAT G G CTG CTTATG TA G ACA ATTCTA G TCTTACTATTAA G AAA CCTAATG A ATTAT
CTA G A GTATTA G G TTTG AAAA
CCCTTG CTACTCATG GTTTAG CTG CTGTTAATAGTGTCCCTTG G G AT ACTATAG CTAATTATGCTAAG
CC TTTT CTTAACAAA
GTTGTTAGTACAACTACTAACATAGTTACACG GTGTTTAAACCGTGTTTGTACTAATTATATG
CCTTATTTCTTTACTTTATTG
CTACAATTGTGTACTTTTACTAGAAGTACAAATTCTAG AATTAAAGCATCTATG CC GACTACTATAG
CAAAGAATACTGTTA
AG A G TG TC G G TAAATTTT G TCTAG AG G
CTTCATTTAATTATTTGAAGTCACCTAATTTTTCTAAACTGATAAATATTATAATT

TG GTTTTTACTATTAAGTGTTTG CCT AG GTTCTTTAATCTACTCAACCG CTG CTTTAG
GTGTTTTAATGTCTAATTTAG G CAT
G CCTT CTTA CTG TACT G G TTA CA G AG AA G G CTATTTGAACTCTACTAATGTCACTATTG
CAACCTACTGTACTG GTTCTATAC
CTTGTAGTGTTTGTCTTAGTG GTTTAGATTCTTTAGACACCTATCCTTCTTTAG
AAACTATACAAATTACCATTTCATCTTTTA
AATG GG ATTTAACTG CTTTTG G CTTAGTTG CAG AG TG GTTTTTG G CATATATTCTTTTCACTAG
GTTTTTCTATGTACTTG GA
TTG G CTG CAATCATG CAATTGTTTTTCAG CTATTTTG CAGTACATTTTATTAGTAATTCTTG G
CTTATGTG GTTAATAATTAAT
CTTGTACAAATG G CCC CGATTTCAG CTATG GTTAGAATGTACATCTTCTTTG CATCATTTTATTATGTATG
G AAAAGTTATGT
G C ATGTTG TA G AC G G TTG TAATTCAT CAACTT G TATG AT G TG TTA CAA AC G TAATAG
AG CAA CAAG A G TC G AATGTACAAC
TATTGTTAATG GTGTTAG AAG G TCCTTTTATGTCTATG CTAATG GAG GTAAAGG CTTTTG
CAAACTACACAATTG GAATTGT
GTTAATTGTG ATACATTCTGTG CT G G TAG TACATTTATTAG TG AT G AAG TTG C G AG AG
ACTTG T CA CTACAG TTTAAAAG AC
CAATAAATC CTACTG AC CAG TCTT CTTACATC G TT G AT AG T G TTAC AG TG AAGAATG
GTTCCATCCATCTTTACTTTG ATAAA
G CTG GT CAAAAG ACTTATG AAA G ACATTCTCTCTCTCATTTTGTTAACTTAGACAACCTG AG AG
CTAATAACACTAAAG G TT
CATTG CCTATTAATGTTATAGTTTTTGATGGTAAATCAAAATGTGAAGAATCATCTG CAAAATCAG
CGTCTGTTTACTACAG
TC AG CTTATGTGTCAACCTATACTGTTACTAG ATCAGG CATTAGTGTCTG ATGTTG GTGATAGTG CG
GAAGTTG CAGTTAA
AATGTTTGATG CTTACGTTAATACGTTTTCATCAACTTTTAACGTACCAATG G AAAAACTC AAAACA CTAG
TT G CAACTG CA
GAAG CTG AACTTG CAAAGAATGTGTCCTTAGACAATGTCTTATCTACTTTTATTTCAG CAGCTCG G CAAG
GGTTTGTTG ATT
CAG ATG TAG AA ACTAAA G AT G TTG TTG AATGTCTTAAATTGTCACATCAATCTG ACATAG
AAGTTACTG G C G ATAG TT G TA
ATAACTATATG CTCACCTATAACAAAGTTG AAAACATG ACACC CC GTG ACCTTG GTG CTTGTATTG
ACTG TAG TG CGCGTCA
TATTAATG CG C AG GTAG CAAAAAGTCACAACATTG CTTTG ATATG G AACGTTAAAG
ATTTCATGTCATTGTCTGAACAACTA
CG AAAACAAATAC G TAG T G CT G CTAAAAAGAATAACTTACCTTTTAAGTTGACATGTG
CAACTACTAGACAAGTTGTTAAT
GTTGTAACAACAAAGATAG CACTTAAG G GTG GTAAAATTGTTAATAATTG GTTGAAG CA G TTAATTAAA
G TTA CACTTG TG
TT CCTTTTTG TTG CTG CTATTTTCTATTTAATAACA CCT GTT CATG T CAT G TCTAAACATACTG
ACTTTTCAAGTG AAATCATA
G GATACAAG G CTATTGATG GTG GTGTCACTCGTG ACATAG C AT CTACA G ATACTTG TTTT G
CTAACAAACATG CT G ATTTTG
ACACATG GTTTAG CCAGCGTG GTG GTAGTTATACTAATGACAAAGCTTG CCCATTGATTG CTG
CAGTCATAACAAG AG AAG
TG G GTTTTGTCGTG CCTG G TTTG CCTG G CACGATATTACG CACAACTAATG GTGACTTTTTG
CATTTCTTACCTAG AG TTTTT
AG T G CAGTTG G TAATATCT G TTAC ACACCATCAAAA CTTATA G AG TACACT G ACTTTG
CAACATCAG CTTGTGTTTTG GCTG
CT G AATG TACAATTTTTAAAG AT G CTTCTG GTAAG CCAGTACCATATTGTTATG ATACC AAT G TA
CTAG AAG G TT CTG TTG C
TTATG AA AG TTTAC G CCCTG ACACACGTTATGTG CT C ATG G ATG G
CTCTATTATTCAATTTCCTAACACCTACCTTG AAG G TT
CTGTTAG AG T G G TAACAACTTTTG ATTCTG AG TACT G TAG G CAC G G CA CTTG TG AAA G
ATC AG AAG CTG G TG TTTG T G TAT
CTACTAG TG GTAGATG G G TACTTAACAATG ATTATTA CAG AT CTTTACCAG G AG TTTT CTGTG
GTGTAG ATG CTGTAAATTT
ACTTACTAATATGTTTACACCACTAATTCAAC CTATTG GT G CTTTG G ACATAT CA G CAT CTATAG
TAG CTG GTG G TATTG TA
G CTATCG TAG TAACAT G CCTTG CCTACTATTTTATG AG G TTTAG AAG AG CTTTTG GTG
AATACAGTCATGTAGTTG CCTTTA
ATACTTTACTATTCCTTATGTCATTCACTGTACTCTGTTTAACACCAGTTTACTCATTCTTACCTG
GTGTTTATTCTGTTATTTA
CTTGTACTTGACATTTTATCTTACTAATG ATGTTTCTTTTTTAG CA CATATT CAG T G G AT G G
TTATGTTCACACCTTTAG TA CC
TTTCTG GATAACAATTG CTTATATCATTTGTATTTCCACAAAG CATTTCTATTG G TTCTTTA G
TAATTACCTAAAG AG AC G TG
TAG TCTTTAAT G G TG TTT CCTTTAG T ACTTTTG AA G AAG CTG CG CTG TG CA CCTTTTTG
TTAAATAAAG AAATGTATCTAAAG
TTG CGTAGTG ATGTG CTATTACCTCTTACG CAATATAATAG ATACTTAG
CTCTTTATAATAAGTACAAGTATTTTAGTG GAG
CAATGGATACAACTAG CTACAG AG AA G CT G CTTGTTGTCATCTCG C AAA G G CTCTCAATG A CTT
CAG TAACTC AG GTTCTG
ATG TTCTTTA CC AAC C AC CAC AAA CCT CTAT CACCT CAG CTGTTTTG CA G AG TG G
TTTTAG AAAAATG G CATTCCCATCTG GT
AAAGTTG AG G GTTG TAT G GTACAAGTAACTTGTG G TA C AACTACACTTAACG GTCTTTG
GCTTGATGACG TAG TTTACT G T
CCAAGACATGTG ATCTGCACCTCTG AAG A CATG CTTAACCCTAATTATGAAG ATTTACTCATTCG
TAAGTCTAATCATAATTT
CTTG GTACAG G CTG G TAAT G TT CAACT CAG G GTTATTGG ACATTCTATG
CAAAATTGTGTACTTAAG CTTAAG GTTGATACA
G CCAATCCTAAG ACACCTAAGTATAAGTTTGTTCG CATT CAA CC AG G AC AG ACTTTTTCAG TG
TTAG CTTG TTAC AATG G TT
CAC CATCT G GTGTTTACCAATGTG CTATG AG G CCCAATTTCACTATTAAG G GTTCATTCCTTAATG G
TT CATG TG G TAG TG T
TG GTTTTAACATAGATTATG ACTGTGTCTCTTTTTGTTACATG CAC CATATG G AATTACCAACTG G AG
TT CATG CTG G CACA
GACTTAG AAG GTAACTTTTATG GAC CTTTTGTTGAC AG G CAAACAG CACAAG CAG CTG GTACG G
ACACAACTATTA CAG TT
AATGTTTTAG CTTG GTTGTACG CTG CT G TTATAAATG G A G ACAG GTG G TTTCTCAAT C G
ATTTACCACAACTCTTAATG ACT
TTAACCTTGTG G CTATG AA G TAC AATTAT G AAC CTCTAA CACAAG ACC ATG TTG AC ATACTAG
G AC CTCTTTCTG CT CAAAC
TG GAATTGCCGTTTTAGATATGTGTG CTTCATTAAAAGAATTACTG CAAAATG G TATG AATG G AC GTAC
CATATTG G G TAG
TG CTTTATTAGAAGATG AATTTACACCTTTTGATGTTG TTAG A C AATG CTCAG GTG
TTACTTTCCAAAGTG CAG TG AAAAG A
ACAATCAAG G G TA CACACC ACTG GTTGTTACTCACAATTTTG ACTTCACTTTTAG TTTTAG TC CAG A
G TA CTCAATG GTCTTT
G TTCTITTTTITG TAT G AAAATG CCTTITTACCTTITG CTATGG GTATTATTG CTATGTCTG CTTTTG
CA ATG ATG TTTG T CAA
AC ATAA G CATG CATTTCTCTGTTTGTTTTTGTTACCTTCTCTTG CCACTG TA G CTTATTTTAATATG
GTCTATATG CCTG CTAG
TTG G GTGATG CGTATTATG ACATG GTTG G ATATG GTTGATACTAGTTTGTCTG GTTTTAAG CTAAA
AG ACTG TG TTATG TAT
G CATCAG CTG TAG TG TTAC TAATCCTTATG AC AG CAAGAACTGTGTATG ATGATG GTG CTAG GAG
AG TG TG G AC ACTTATG
AAT G TCTTG A CACTC G TTTATAAA G TTTATTATG GTAATG CTTTAGATCAAG CCATTTCCATGTG
GG CTCTTATAATCTCTGT

TACTTCTAACTACTCAG G TG TAG TTAC AACTG TCAT G TTTTTG G CCA G AG G TATT G
TTTTTATG T G TG TTG AG TATTG CC CTA
TTTTCTTCATAACTG GTAATACACTTCAGTGTATAATG CTAGTTTATTGTTTCTTAG G
CTATTTTTGTACTTGTTACTTTG G CC
TCTTTTGTTTACTCAACCG CTACTTTAGACTGACTCTTG GTGTTTATGATTACTTAGTTTCTACACAG G AG
TTTA G ATATATG
AATTCACAG G G ACTACTCC CAC CCAAG AATA G CATAGATG CCTTCAAACTCAACATTAAATTG TTG G
GTGTTG GTG G CAAA
CCTTG TATCAAAG TAG CCACTG TACAG T CTAAAATG T CAG AT G TAAAG TG CACAT CAG TAG T
CTTA CTCTC AG TTTTG CAAC
AACT CAG AG TAG AATCATCATCTAAATTGTG GG CT CAATG TGTCCAGTTACACAATG ACATTCTCTTAG
CTAAAGATACTAC
TG AAGCCTTTGAAAAAATG GTTTCACTACTTTCTGTTTTG CTTTCCATG CA G G GTG CT G TAG
ACATAAACAAG CTTTG T G AA
GAAATG CTG G AC AACAG G G CAACCTTACAAG CTATAG CTT CAG AG TTTA G TTC CCTTC
CATCATATG CA G CTTTTG CTACTG
CT CAAG AAG CTTATG AG CA G G CTG TT G CTAATG GTGATTCTGAAGTTGTTCTTAAAAAGTTG AAG
AA G TCTTTG AATGTG G
CTAAATCTGAATTTGACCGTGATG CAG C CATGCAACG TAAGTTG G AAAAGATG G CTG AT CAAG
CTATG ACCCAAATG TATA
AAC AG G CTAG AT CTG AG G AC AAG AG G G CAAAAGTTACTAGTG CTATGCAGACAATG
CTTTTCACTATG CTTAG AAA G TT G
GATAATG ATG CA CTCAAC AACATTATCAACAATG CAAG A G ATG GTTGTGTTCCCTTG
AACATAATACCTCTTACAACAG CA
G CCAAACTAATG GTTGTCATACCAG ACTATAACACATATAAAAATACGTGTGATG G TAC AA
CATTTACTTATG CATC AG CAT
TGTG GG AAATCCAACAG GTTG TAG AT G CA G ATAG TAAAATTG TT CAACTTAG T G AAATTAG
TATG G ACAATTCACCTAATT
TAG CATG GCCTCTTATTGTAACAG CTTTAAGG G CCAATTCTG CTGTC AAATTACAG AATAATG AG
CTTAGTCCTG TTG CA CT
ACG ACAGATGTCTTGTGCTG CC G G TACT ACACAAACTG CTTG CACTG ATG AC AATG CGTTAG
CTTACTACAACACAACAAA
G G GAG G TAG GTTTGTACTTG C ACTG TTAT CC G ATTTACAG GATTTG AAATG G G CTAG ATTC
CCTAAG AG T G AT G GAACTG
GTACTGTCTATACAG AACTG G AACC ACCTT G TA G GTTTGTTACAG ACACACCTAAAG GTCCTAAAGTG
AAGTATTTATACTT
TATTAAAG GATTAAACAACCTAAATAG AG GTATG GTACTTG GTAGTTTAG CTG C CACA G TA C GT
CTAC AAG CT G GTAATG C
AAC AG AAG TG CCTG CC AATT CAACTG TATTATCTTTCTG TG CTTTTG CTG TA G ATG CTG
CTAAAG CTTACAAAG ATTATCTA
G CTAGTG GGGG AC AACCAATCACTAATTGTG TTAAG ATG TTGTGTA CACACA CTG GTACTG GTCAG
G CAATAACAGTTACA
CCG GAAG CCAATATG GATCAAG AATCCTTTG GTG GTG CATCGTGTTGTCTGTACTG CCGTTG
CCACATAGATCATCCAAAT
CCTAAAG GATTTTGTG ACTTAAAAG GTAAGTATGTACAAATACCTACAACTTGTG CTAAT G AC CCTGTG G
GTTTTACACTTA
AAAACACAGTCTGTACCGTCTG CG GTATGTG G AAAG GTTATG G CTGTAGTTGTGATCAACTCCG
CGAACCCATG CTTCAGT
CAG CTG ATG CACAATCGTTTTTAAACG G GTTTG C G GT GTAAG TG CAG CCCGTCTTACACCGTG CG
GCACAG G CACTAGTAC
TG ATGTCGTATACAG G G CTTTTG AC ATCTACAAT G ATAAAGTAG CT G GTTTTG
CTAAATTCCTAAAAACTAATTGTTGTCG C
TTCCAAG AAAAG G ACGAAGATG ACAATTTAATTGATTCTTACTTTGTAGTTAAG AG
ACACACTTTCTCTAACTACCAACATG
AAG AAACA ATTTATAATTTA CTTA AG GATTGTCCAG CTG TT G CTAAACATG ACTT CTTTAAG
TTTAG AATAG AC G GTG AC AT
G GTACCACATATATCACGTCAACGTCTTACTAAATACACAATG G CAG AC CTC G T CTAT G CTTTAAG G
CATTTTG ATG AAG GT
AATTGTG ACACATTAAAAGAAATACTTGTCACATACAATTGTTGTG ATG AT G ATTATTT CAATAAAAAG G
ACTG G TAT G ATT
TT G TAG AAAACCC AG ATATATTAC G CGTATACG CCAACTTAG G TG AA C G TG TAC G CCAAG
CTTTGTTAAAAACAGTACAAT
TCTGTG ATG C CATG CG AAATG CTG GTATTGTTG G TG TACTG A CATTAG ATAATCAAG
ATCTCAATG G TAA CT G GTATG ATTT
CG GTGATTTCATACAAACCACG CCAG G TA G TG G AG TTCCTG TT G TA G ATTCTTATTATTCATTG
TTAAT G CCTATATTAACC
TT G ACCA G G G CTTTAACTG CA G AG T CACATG TTG ACACTG ACTTAACAAAG
CCTTACATTAAGTG G GATTTG TTAAAATAT
GACTTCACG G AAG A G AG G TTAAAACTCTTTG ACC G TTATTTTAAATATTG G G AT CAG A
CATAC CACCCAAATTG TG TTAACT
GTTTG G ATG A CAG AT G CATTCTG CATTGTG CAAACTTTAATG TTTTATTCTCTAC AGTG TT CC
CACTTACAAG TTTT G G AC CA
CTAGTG AG AAAAATATTTG TTG ATG GTGTTCCATTTG TAG TTTCAACTG G ATACCA CTTCAG AG AG
CTAG GTGTTGTACATA
ATC AG G ATG TAAACTTACATA G CTCTAGACTTAGTTTTAAG G AATTACTTGTGTATG CTG CT G ACC
CTG CTATG CAC G CTG C
TT CTG GTAATCTATTACTAG ATAAACG CA CTAC G TG CTTTT CAG TAG CTG
CACTTACTAACAATGTTG CTTTTCAAACTGTCA
AACCCG GTAATTTTAACAAAGACTTCTATG ACTTTG CTGTGTCTAAG G GTTTCTTTAAG GAAG G AA
GTTCTG TTG AATTAAA
ACACTTCTTCTTTG CTCAG GATG GTAATG CT G CTATCAG C G ATTATG A CTACTATC G TTATAAT
CTACCAAC AATG TGTG ATA
TCAGACAACTACTATTTGTAGTTG AAGTTGTTG ATAAGTACTTTG ATTGTTACG ATG GTG G
CTGTATTAATG CTAACCAAGT
CATCGTCAACAAC CTAG AC AAATCAG CTG GTTTTCCATTTAATAAATG G G GTAAG G CTAG
ACTTTATTATG ATTCAATG AG T
TAT G AG G ATCAAGATG CACTTTTCG CATATACAAAAC G TAATG T CATC CCTACTATAA CTCAAAT
G AAT CTTAAG TATG CC A
TTAGTG CAAAGAATAG A G CT C G CAC C GTA G CTG G T G TCTCTATCTG TA G TACTATG
ACCAATAGACAGTTTCATCAAAAAT
TATTGAAATCAATAG CCG C CACTAG AG G AG CTACTG TAG TAATTG GAACAAG CAAATTCTATGGTG
GTTG G CACAACATGT
TAAAAACTG TTTATAG TG AT G TAG AAAACCCTCACCTTATG G GTTG G GATTATCCTAAATGTG ATAG
AG CCATG CCTAACA
TG CTTAG AATTATG G CCTCACTTG TTCTTG CT CG CAAACATACAACG TG TTG TA G CTT G TCA
CACC G TTT CTATA G ATTAG CT
AATGAGTGTG CTCAAGTATTGAGTGAAATGGTCATGTGTG G CG GTTCACTATATGTTAAACCAG GTG
GAACCTCATCAGG
AG ATG C CACAA CTG CTTATGCTAATAGTGTTTTTAACATTTGTCAAG CTG TCACG G CCAATGTTAATG
CACTTTTATCTACTG
ATG GTAACAAAATTG CCG ATAAGTATGTCCG CAATTTA CAA CA CA G A CTTTATG A G TG T
CTCTATA G AA ATA G A G ATG TTG
ACAC AG ACTTTG T G AATG AG TTTTAC G CATATTTG C GTAAACATTTCTCAATG AT G ATA CTCT
CTG A C G ATG CTGTTGTGTG
TTTCAATAG CA CTTAT G C AT CTC AAG GTCTAGTGG C TAG CATAAAG AACTTTAAG T CAG TT
CTTTATTAT CAAAA C AAT G TTT
TTATGTCTGAAG CAAAATGTTG GACTG AG ACT G ACCTTACTAAAG G ACCTCATG AATTTTG CT
CTCAACATAC AATG CTAGT
TAAACAG G GTG ATG ATTATGTG TACCTT CCTTACCC AG ATCCATC AAG AATCCTAG G G G CCG G
CT GTTTTG TAG ATG ATAT

CG TAAAAA CAG AT G GTACACTTATG ATTG AACG GTTCGTGTCTTTAG CTATAGATG
CTTACCCACTTACTAAACATCCTAAT
CAG G A GTATG CTG AT GTCTTTC ATTT GTACTTACAATACATAAG AAAG CTACATG ATG AG
TTAACAG G ACACATGTTA G AC
ATGTATTCTGTTATG CTTACTAATGATAACACTTCAAG GTATTG G GAACCTGAGTTTTATG AG G
CTATGTACACACCG CATA
CAGTCTTACAG G CTGTTG G G G CTTGTGTTCTTTG CAATTCAC AG ACTTCATTAAG ATG TG GTG
CTTG CATACGT AG ACC ATT
CTTATGTTGTAAATG CTGTTACG ACCATGTCATATC AACATC AC ATA AATTA GTCTTGT CTGTTAATC
CGTATGTTTG CAATG
CTCCAG GTTGTGATGTCACAG ATGTGACTCAACTTTACTTAG G AG GTATGAG CTATTATTG TAAAT
CACATAAACCACC CAT
TAG TTTTCCATTGT G TG CTAATG G A CAAGTTTTTG GTTTATATAAAAATACATGTGTTG GTAG CG
ATAATGTTACTGACTTTA
ATG CAATTG CAACATG TGACTG G ACAAAT G CT G GTG ATTACATTTTAG CTAACACCTGTACTG AAA
G ACT CAAG CTTTTTG C
AG C AG AAA CG CT CAAAG CTACTG AG G AGACATTTAAACTGTCTTATG GTATTG
CTACTGTACGTGAAGTG CT G TCT G ACAG
AGAATTACATCTTTCATG G G AA GTTG G TAAAC CTAG ACCA C CA CTTAACCG
AAATTATGTCTTTACTG GTTATCGTGTAACT
AAAAACAGTAAAGTACAAATAG G AG AG TACACCTTTG AAAAAG GTG ACTATG GTG ATG
CTGTTGTTTACCG AG GTACAAC
AACTTACAAATTAAATGTTG G TG ATTATTTTGT G CT G ACAT CACATACAGTAATG CCATTAAGTG CAC
CTACACTAGT G CCA
CAAG AG CA CTAT GTTA G AATTACTG G CTTATAC CCAACA CTC AATATCTCATAT GAG TTTT
CTAG CAATGTTG CAAATTATC
AAAAG GTTG GTATG CAA AAGTATTCTACACT CCA G G GACCACCTGGTACTG GTAAG AGTCATTTTG
CTATTGG CCTAG CTC
TCTACTACCCTTCTG CTCG CATAGTG TATAC AG CTTG CT CTCATGCC GCT GTTG ATG
CACTATGTGAGAAG G CATTAAAATA
TTTGCCTATAG ATAAATGTAGTAG AATTATACCTG CACGTG CTCG TGTAG AG TGTTTTG
ATAAATTCAAAGTG AATTCAACA
TTAG AA CAG TATG TCTTTTGT ACTGTAAATG CATTG CCT G AG AC G ACAG
CAGATATAGTTGTCTTTGATG AAATTTCAATG G
CCACAAATTATG ATTTGAGTGTTGTCAATG CCAGATTACGTG CTAAG CA CTATG TGTACATTG G CG ACC
CTG CTCAATTACC
TG CACCACG CAC ATTG CTAACTAAG G G CAC ACTAG AACCAG
AATATTTCAATTCAGTGTGTAGACTTATGAAAACTATAG G
TCCAGACATGTTCCTCG GAACTTGTCG G CGTTGTCCTG CTGAAATTGTTGACACTGTG AG TG CTTTG
GTTTATG ATAATAAG
CTTAAAG CACATA AAG AC AAATCA G CTCAATG CTTTAAAATGTTTTATAAG G GTGTTATCACG CAT G
ATG TTTC ATCT G CAA
TTAACAG GCCACAAATAG G CGTG GTAAG AG AATTCCTTACACG TAACC CTG CTTG G AG AAAAG CT
GTCTTTATTTC ACCTT
ATAATTCACAGAATG CT GTAG CCTCAAAGATTTTG G G ACTACCAACTCAAACTGTTG ATTCATCACAG G
G CT CAG AATATG
ACTATGTCATATTCACTCAAACCACTG AAA CAG CTCACTCTTGTAATGTAAACAGATTTAATGTTG
CTATTACCAG A G C AAA
AGTAGG CATACTTTG CATAATG TCTG ATAG AG ACCTTTATG ACAAGTTG CAATTTACAAG
TCTTGAAATTCCAC GTAG GAAT
GTG G CAACTTTACAAG CTGAAAATGTAACAG G ACTCTTTAAAGATTGTAGTAAGGTAATCACTG G
GTTACATCCTACACAG
G CACCTACACACCTCAGTGTTG ACACTAAATTCAAAACTGAAG GTTTATGTGTTGACATACCTG
GCATACCTAAG G AC ATG
ACCTATAG AAGACTCATCTCTATGATG G GTTTTAAAATG AATTATCAAGTTAATG
GTTACCCTAACATGTTTATCACCCG CG
AAG AAG CTATAAGACATGTACGTG CATG GATTG G CTTCG ATG TCG AG G G GTGTCATG CTACTAG
AG AAG CTGTTG GTACC
AATTTACCTTTACAG CTAGGTTTTTCTACAG GTGTTAACCTAGTTG CTGTACCTACAG G TTATG TT G
ATACACCTAATAATAC
AGATTTTTCCAGAGTTAGTG CTAAACCACCG CCTG G AG AT CAATTTAAACACCTC
ATACCACTTATGTACAAAG G ACTTC CT
TG GAATGTAGTG CG TATAAAGATTGTACAAATGTTAAG TG ACA CACTTAAAAATCTCTCTG AC AG
AGTCGTATTTGTCTTAT
G G G CAC ATG G CTTT G AG TTG AC ATCTATG AAG TATTTTG TGAAAATAG G ACCT GAG CG
CACCTGTTGTCTATGTGATAG AC
GTG CCACATG CTTTTCCACTG CTTCAG ACACTTATG CCTGTTG G CAT CATTCTATTG G ATTTG
ATTACGTCTATAATCCGTTT
ATG ATTG ATGTTCAACAATG G G GTTTTACAG GTAACCTACAAAG CAACCATG AT CTG TATT
GTCAAGTC C ATG GTAATG CA
CATGTAG CTAGTTGTG ATG CAATCATGACTAGGTGTCTAG CTGTCCACGAGTG CTTTGTTAAG CGTGTTG
ACTG GACTATT
GAATATCCTATAATTG GTG ATGAACTG AAGATTAATG CG G CTTG TAG AAAG GTTCAACACATG
GTTGTTAAAG CTG CATTA
TAG CAG ACAAATTCCCAG TTCTT CAC GAC ATTG GT AAC CCTAAAG CTATTAAGTG TGTACCTCA AG
CT G ATG TAG AAT G G
AAGTTCTATG ATG CAC AG CCTTGTA GTG A CAAAG CTTATAAAATAG AAGAATTATTCTATTCTTATG C
C AC ACATTCTG ACA
AATTCACAGATG GTGTATG CCTATTTTG GAATTG CAATGTCGATAGATATCCTG CTAATTCCATTGTTTG
TAG ATTTG ACACT
AGAGTG CTATCTAACCTTAACTTG CCTG GTTGTGATG GTG G CAGTTTGTATGTAAATAAACATG
CATTCCACACACCAG CTT
TT G ATAAAAG TG CTTTTGTTAATTTAAAACAATTACCATTTTTCTATTACTCTGACAGTCCATGTG
AGTCTCATG GAAAACAA
GTAGTGTCAG ATATAGATTATG TAC CA CTAAAGT CT G CTACGTGTATAACACGTTG CAATTTAG GT G
GIG CTGT CTG TAG A
CAT C ATG CTAAT G AGT ACA GATTG TATCT CG AT G CTTATAAC ATG ATG AT CTCAG CTG G
CTTTAG CTTGTG G GTTTACAAAC
AATTTGATACTTATAACCTCTG G A ACACTTTT ACAA G ACTT CAG AGTTTAGAAAATGTG G
CTTTTAATGTTGTAAATAAG G G
ACACTTTGATG GACAACAG G GTG AAGTAC CAGTTTCTATCATTAATAACACTGTTTACACAAAAGTTGATG
GTGTTG ATGT
AGAATTGTTTGAAAATAAAACAACATTACCTGTTAATGTAGCATTTG AG CTTTG G GCTAAG CG CAA
CATTAAACC AG TACC
AGAG GTGAAAATACTCAATAATTTG G GTGTG G ACATTG CTG CTAATACTGTGATCTGG G ACTACAAAAG
AG ATG CTCCAG
CAC ATATATCTACTATTG GTGTTTGTTCTATG ACTGACATAG CCAAG AAACCAACTGAAACGATTTGTG
CACCACTCACTGT
CTTTTTTGATG GTAGAGTTGATG GTCAAGTAGACTTATTTAG AAATG C CC G TAATGGTGTTCTTATTACAG
AAG GTAGTGTT
AAAG G TTTA CAA CCATCTGTA G GTCCCAAACAAG CTAGTCTTAATG G AG TCA CATTAATT G G AG
AAG CCG TAAAAA CA CA G
TT CAATTATTATAAG AAAGTTGATG GTG TTG TCCAA CAATTACCT GAAACTTACTTTACTC AG AGTAG
AAATTTACAAGAAT
TTAAACCC AG GAG TCAAATG GAAATTG ATTTCTTAG AATTAG CTATGGATGAATTCATTG AACG
GTATAAATTAG AAG G CT
ATG CCTTCG AA CATATCGTTTATG G AG ATTTTAGTC ATAGTCAGTTAG GTG GTTTACATCTACTG
ATTG GACTAG CTAAACG
TTTTAAG G AAT CA CCTTTTG AATTAGAAG ATTTTATTCCTATG G A CAGTA CAG TTAAAAA
CTATTTCATAACAG ATG CG CAA

ACAG G TT CATCTAAG T G TG TGTGTTCTGTTATTGATTTATTACTTGATG
ATTTTGTTGAAATAATAAAATCCCAAG ATTTATC
TG TAG TTTCTAAG GTTGTCAAAGTGACTATTGACTATACAG AAATTTCATTTATG CTTTGGTGTAAAGATG G
C C ATG TAG AA
ACATTTTACCCAAAATTACAATCTAGTCAAG CGTG G CAACCG G GTGTTG CTATG
CCTAATCTTTACAAAATG CAAAGAATG C
TATTAG A AAAGT G TG A CCTT CAAAATTATG GTG ATAGTG CAACATTACCTAAAG G CATAATG
ATGAATGTCGCAAAATATA
CTCAACTGTGTCAATATTTAAACACATTAACATTAG CTGTACCCTATAATATG AG AG TTATACATTTTG GTG
CTGG TTCTG AT
AAA G G AG TTG C ACC AG G TAC AG CTGTTTTAAG ACAGTG GTTG CC TAC G G G TA C G CT
G CTT GT C G ATTC AG AT CTTAATG AC
TTTGTCTCTG AT G C AG ATTCAACTTTG ATTG GTG ATTGTG CAACTGTACATACAGCTAATAAATG G G
AT CT CATTATTAG TG
ATATGTACGACCCTAAGACTAAAAATGTTACAAAAG AAAATG ACTCTAAAG AG G
GTTTTTTCACTTACATTTGTG G GTTTAT
ACAACAAAAG CTAG CT CTT G G AG GTTCCGTG G CTATAAAGATAACAG AACATTCTTGG AATG CTG
AT CTTTATAAG CTCAT
G G G AC ACTTCG CATG GTG GACAG CCTTTGTTACTAATGTG AATG CGTCATCATCTG AAG
CATTTTTAATTG GATGTAATTAT
CTTG G CAAACCACGCG AACAAATAGATG GTTATGTCATG CATG CAAATTACATATTTTGG AG
GAATACAAATCCAATTCAG
TT G TCTTCC TATTCTTTATTTG ACATG AG TAAATTTCCC CTTAAATTAAG G G GTACTG CT G
TTATG T CTTTAAAAG AAG GTCA
AATCAATG ATATG ATTTTATCTCTTCTTAGTAAAG G TAG ACTTATAATTAG AG AAAACAACA G AG TTG
TTATTT CTAG TG AT
GTTCTTGTTAACAACTAAACG AACAATGTTTGTTTTTCTTGTTTTATTG
CCACTAGTCTCTATTCAGTGTGTTAATCTTACAAC
CAG AACTCAATTACCCCCTG CATACACTAATTCTTTCACACGTG GTGTTTATTACCCTGACAAAGTTTTCAG
ATCCTCAGTTT
TAC ATTCAACTC AG G A CTTG TTCTTACCTTTCTTTT CCAAT G TTA CTTG GTTCCATG
CTATACATGTCTCTGG GACCAATG GT
ACTAAG AG GTTTGATAACCCTGTCCTACCATTTAATGATG GT GTTTATTTTG CTTCCACTG AGAAGTCTAA
CATAATAAG AG
G CTG GATTTTTG G TACTACTTTAG ATTC G AAG ACC C AG T CCCTACTTATT G TTAATAAC G
CTACTAATGTTGTTATTAAAGTC
TGTGAATTTCAATTTTGTAATGATCCATTTTTG G GTGTTTATTACCACAAAAACAACAAAAGTTGTATG G
AAAGTGAGTTCA
G AG TTTATTCTAGTG CG AATAATTG CACTTTTGAATATGTCTCTCAG CCTTTTCTTATGGACCTTG AAG G
AAAAC AG G GTAA
TTTCAAAAATCTTAG G GAATTTGTGTTTAAGAATATTGATG GTTATTTTAAAATATATTCTAAG C AC ACG
CCTATTAATTTAG
TG CGTG ATCT CCCTC AG G G TTTTTCG G CTTTAGAACCATTG GTAGATTTG CCAATAG
GTATTAACATCACTAGG TTTCAAAC
TTTACTTG CTTTACATAG AAG TTATTTG A CTCCTG GTG ATT CTTCTTC AG GTTG GACAG CTG GTG
CTG CAG CTTATTATGTG G
GTTATCTTCAACCTAG GACTTTTCTATTAAAATATAATGAAAATG G AACCATTACA G AT G CTG TA G
ACT G TG CACTTG ACCC
TCTCTCAG AAACAAAG TG TAC G TTG AAATCCTT CACT G TAG AAAAAG G AATCTATCAAA
CTTCTAACTTTAG AG TCCAAC CA
ACAG AATCTATT G TTA G ATTTCCTAATATTAC AAA CTTG TG CC CTTTTG GTG AA G TTTTTAA C
G CCACCAGATTTG CATCTGT
TTATG CTTG GAACAG GAAGAGAATCAG CAACTGTGTTG CTG ATTATTCTGTCCTATATAATTCCG
CATCATTTTCCACTTTTA
AG T G TTATG G AG TG TCTC CTACTAAATTAAATG ATCT CTG CTTTA CTAAT G TCTATG C AG
ATTC ATTTG TAATTA G AG G TG AT
G AA G TCA G ACAAATCG CTCCAG G G CAAACTG GAAAG ATTG CT G ATTATAATTATAAATTA
CCAG ATG ATTTTA CAG G CTG C
GTTATAG CTTG GAATTCTAACAATCTTGATTCTAAG GTTG GTG GTAATTATAATTACCG GTATAG
ATTGTTTAG G AA G T CTA
ATCTCAAACCTTTTG AG AG AG ATATTTCAACTG AAATCTATCAG G CC G GTAG CAC ACCTTGTAATG
GTGTTGAAG GTTTTAA
TTGTTACTTTCCTTTACAATCATATG GTTTCCAACCCACTAATGGTGTTGGTTACCAACCATACAG AG TAG TAG
TACTTT CTT
TT G AACTTCTA CATG CACCAG CAACTGTTTGTG G AC CTAAAAAG TCTA CTAATTT G
GTTAAAAACAAATGTGTCAATTTCAA
CTTCAATG GTTTAACAG G CACAGGTGTTCTTACTGAGTCTAACAAAAAGTTTCTG CCTTTCCAACAATTTG G
CAG AG ACATT
G CTGACACTACTG ATG CTGTCCGTG ATC CACAG A CACTTG AG ATTCTTG AC ATTACACCATG
TTCTTTTG GTG GTGTCAGTG
TTATAACACCAG G AACAAATACTTCTAACCAG G TT G CTGTTCTTTATCAG G
GTGTTAACTGCACAGAAGTCCCTGTTG CTAT
TCATG CAG AT CAACTTACTCCTACTTG GC GTG TTTATTCTA CAG GTTCTAATGTTTTTCAAACACGTG
CAG GCTGTTTAATAG
G G G CTG AACAT G TCAACAACT CATAT G AG T G TG ACATA CCCATTG GTGCAG GTATATG CG
CTAGTTATCAG ACTCAG ACTA
ATTCTCCTCG G CG G G CACG TAG TG TAG CTAG TCAATC CAT CATTG CCTACACTATGTCACTTG
GTG CAG AAAATTCAGTTG C
TTACTCTAATAACTCTATTG CCATAC CCACAAATTTTACTATTAG TGTTAC
CACAGAAATTCTACCAGTGTCTATG ACCAAG A
CAT C AG T AG ATTG TA C AATG TA CATTTG TG GTGATTCAACTG AATG CA G CAATCTTTTGTTG
CAATATG G CA G TTTTTG TAC
ACAATTAAAC CGTG CTTTAACTG G AATAG CTG TTG AACAAG ACAAAAAC ACC CAAG AAGTTTTTG
CACAAGTCAAACAAAT
TTACAAAACACCACCAATTAAAGATTTTG GTG GTTTTAATTTTTCACAAATATTACCAG ATCCATCAAAACCAAG
CAAG AG G
TCATTTATTG AAG AT CTACTTTT CAA CAA AG TG ACACTTG C A G ATG CTGG
CTTCATCAAACAATATG GTGATTG CCTTG GTG
ATATTG CTG CTAG AG ACCTCATTTGTG CACAAAAGTTTAACG G CCTTACTGTTTTG CCACCTTTG CT
CACAG AT G AAAT G AT
TG CT CAATACACTTCTG CACTGTTAG CG G GTACAATC ACTT CTG GTTG GACCTTTG GTG CAG GTG
CTG CATTACAAATACCA
TTTGCTATG CAAATG G CTTATAG GTTTAATG GTATTGG AG TT ACACA G AAT G TT CTCTATG AG
AACCAAAAATTGATTG CCA
ACC AATTTAATAG CG CTATTG G CAAAATTCAAGACTCACTTTCTTCCACAG CAAGTG CACTTG G
AAAACTT CAA G ATGTGGT
CAACCAAAATGCACAAG CTTTAAACACG CTTGTTAAACAACTTAG CTCCAATTTTG GTG CAATTT CAAG TG
TTTTAAAT G AT
ATC CTTT CAC G TCTT G ACAAA GTT G AG G CTG AAGTG CAAATTG ATAG GTTG ATCAC AG G
CAG ACTTCAAAG TTTG C AG ACA
TAT G TG A CTCA A CAATTAATTA G A G CTG CA G AAAT CA G A G CTICTG CTAATCTIG CTG
CIA CTAA AATG T CA G AG TGT G TA C
TT G G AC AATCAAAAAG AG TTG ATTITIGTG G AAAG G G CTATCATCTTATGICCITCCCICAGICAG
CAC CT CATG G T G TAG T
CTT CTT G CATG TG A CTTAT G TC CCTG CACAAG AAAAG AACTTCACAACTG CTCCTG CCATTTG
T CAT G ATG G AAAAG CAC AC
TTTCCTCGTG AAG GTGTCTTTGTTTCAAATG G CACACACTG GTTTGTAACACAAAG
GAATTTTTATGAACCACAAATCATTA
CTACAGACAACACATTTGTGTCTG GTAACTGTGATGTTGTAATAG
GAATTGTCAACAACACAGTTTATGATCCTTTG CAACC

TG AATTAG ACTCATTCAAG GAG GAGTTAGATAAATATTTTAAG AAT CATAC ATCACC AG ATG TTG
ATTTAGGTGACATCTCT
G G CATTAATG CTT C AG TT GTAAA CATT CAAAAA G AAATTG AC CG CCTCAAT G AG G TTG
CCAAGAATTTAAATGAATCTCTC
ATCGATCTCCAAG AACTTG GAAAGTATGAGCAGTATATAAAATG G CCATG GTACATTTG G CTAG
GTTTTATAG CTG G CTTG
ATTG CCATAGTAATG GTGACAATTATG CTTTG CTGTATG ACC AG TTG CTGTAGTTGTCTCAAG G
GCTGTTGTTCTTGTG G AT
CCTG CTG CAAATTTG ATG AA G ACG ACTCTG AG CCAGTG CTCAAAGG A GTC AAATTA CATTACAC
ATAAAC G AACTTATG G A
TTTGTTTATG AG AATCTT CACAATTG G AACTGTAACTTTG AAGCAAG GTGAAATCAAG GATG
CTACTCCTTCAGATTTTGTT
CG CG CTACTG CAACGATACCGATACAAG CCTCACTCCCTTTCG G ATGG CTTATTGTTG G CGTTG CA
CTTCTTG CTGTTTTTCA
TAG CGCTTCCAAAATCATAACC CTCAAAAAG AG ATG G CAACTAG CACTCTCCAAG G
GTGTTCACTTTGTTTG CAACTTG CTG
TTGTTGTTTGTAACAGTTTACTCACACCTTTTG CTCGTTG CTGTTG G CCTTGAAG
CCCCTTTTCTCTATCTTTATG CTTTAGTC
TACTTCTTG CAG AG TATAAACTTTGTAAG AATAATAATG AG G CTTTG G CTTTG CTG
GAAATGCCGTTCCAAAAACCCATTAC
TTTATG ATG CCAACTATTTTCTTTG CTG G
CATACTAATTGTTACGACTATTGTATACCTTACAATAGTGTAACTTCTTCAATTG
TCATTACTTCAG GTG ATG G CACAACAAGTCCTATTTCTGAACATGACTACCAGATTG GTG
GTTATACTGAAAAATG G GAAT
CTG G AG TAAAA G ACTGTGTTGTATTACACAGTTACTTCACTTCAG ACTATTACC AG CT
GTACTCAACTCAATTG A GTACAG A
CACTG G TGTT G AACATGTTACCTTCTT CATCTACAATAAAATTGTTG AT G AG C CTG AAG AAC
ATGT CC AAATTCACACAATC
G AC G GTTCATCCG G AGTTGTTAATCCAGTAATG G AACCAATTTATG AT G AAC C GACG ACG
ACTACTAG CGTG CCTTTGTAA
G CACAAG CTG ATG A G TACG AACTTATG TACT CATTC GTTTCG G AA G AG AC AG
GTACGTTAATAGTTAATAG CGTACTTCTT
TTTCTTG CTTTCGTGGTATTCTTG CTAGTTACACTAG CCATCCTTACTG CG CTTCGATTGTGTG CG TACT
G CTG CAATATTG TT
AACGTGAGTCTTGTAAAACCTTCTTTTTACGTTTACTCTCGTGTTAAAAATCTGAATTCTTCTAGAGTTCCTGATCTTC
TG GTC
TAAACG AA CTAAATATTATATTAGTTTTTCTG TTTG G AACTTTAATTTTAG CCATG G CAGATTCCAACG
GTACTATTACCG TT
G AAG AG CTTAAAAAGCTCCTTGAACAATG GAACCTAGTAATAG GTTTCCTATTCCTTACATGG
ATTTGTCTTCTACAATTTG
CCTATG C CAA CA G GAATAG GTTTTTGTATATAATTAAGTTAATTTTTCTCTG G CTGTTATG G CC
AGTAACTTTAG CTTGTTTT
GTG CTTG CTG CTG TTTAC AG AATAAATTG G AT CACCG GTG G AATTG CTATCG CAATG G
CTTGTCTTG TAG G CTTG ATGTG G
CTCAG CTACTTCATTG CTTCTTTC AG ACTGTTTG CG CGTACGCGTTCCATGTG GT CATTC AATCCAG
AAA CTAACATT CTTCT
CAA CGTG CCACT C CAT G G CA CTATT CTG ACCAG ACCG CTTCTAGAAAGTGAACTCGTAATCG G
AG CT GTG ATCCTTCG TG G
ACATCTTCGTATTG CTG G A CACCATCTAG GACG CTG TG AC ATCAAG GACCTG CCTAAAG
AAATCACTGTTG CTACATCACG
AACG CTTTCTTATTACAAATTG G G AG CTTCG C AG CGTGTAGCAG GTG ACTCAG GTTTTG CTG
CATACAGTCG CTACAG GAT
TG G CAACTATAAATTAAAC ACAG ACCATTCCAG TAG CAGTG ACAATATTG CTTTG
CTTGTACAGTAAGTG AC AACAG ATG T
TT CATCT CGTTG ACTTTCAG GTTACT ATA G C AG AG ATATTACTAATTATTATG AG G A
CTTTTAAAGTTT CCATTTG G AATCTT
GATTACATCATAAACCTCATAATTAAAAATTTATCTAAGTCACTAACTG AG AATAAATATTCT C AATTAG ATG
AAG AG CAA C
CAATGG AG ATTGATTAAACG AACATGAAAATTATTCTTTTCTTG G CACTGATAACACTCG CTACTTGTG AG
CTTTATC ACTA
CCAAGAGTGTGTTAG AG GTACAACAGTACTTTTAAAAG AACCTTG CT CTT CTG G AACATACG AG G G
CAATTCACCATTTCA
TC CT CTAG CTG ATAACAAATTTG CACTGACTTG CTTTAG CACTCAATTTG CTTTTG CTTGTCCTGACGG
CGTAAAACACGTCT
ATCAGTTACGTG CCAGATCAGTTTCACCTAAACTGTTCATCAGACAAG AG G AAG TTCAAG AACTTTA CT
CTCCAATTTTT CTT
ATTGTTG CG G CAATAGTGTTTATAACACTTTG CTTCACACTCAAAAGAAAG ACAGAATGATTG AA CTTT
CATTAATTG ACTT
CTATTTGTG CTTTTTAG CCTTTCTG CTATTCCTTGTTTTAATTATG CTTATTATCTTTTG GTTCTCACTTG
AA CTG C AAG AT C AT
AATGAAACTTGTCACG CCTAAACTAACATGAAATTTCTTGTTTTCTTAG G AATCATCACAACTGTAG CT G
CATTTCACCAAG
AATGTAGTTTACAGTCATGTACTCAACATCAACCATATGTAGTTG
ATGACCCGTGTCCTATTCACTTCTATTCTAAATG GT AT
ATTAG AG TAG G AG CTAG AAAATCAG CACCTTTAATTGAATTGTG CGTGG ATG AG G
CTGGTTCTAAATCACCCATTCAGTAC
ATCGATATCG GTAATTATACAGTTTCCTGTTTACCTTTTACAATTAATTG CCAG GAACCTAAATTG G G TA G
TCTT GTAG TG C
GTTGTTCGTTCTATG AAG ACTTTTTAG AGTATCATGACGTTCGTGTTGTTTTAGATTTCATCTAAACG
AACAAACTATAATGT
CT G ATAATG G ACCCC AAAATC AG CG AAATG CA CCCC G CATTACGTTTG GTG
GACCCTCAGATTCAACTG G CAG TAACC AG A
ATG GAG AACG CAGTG G G G CG CG ATCAAAACAACGTCG G CC C CAAG GTTTACCCAATAATACTG
CGTCTTG GTTCACCG CT
CTC A CTCAACATG G CAA G GAAG A CCTTAAATTCCCTCGAG GACAAG G
CGTTCCAATTAACACCAATAG CAGTCCAG ATG A C
CAAATTG G CTACTACC G AAG AG CTACCAG ACGAATTCGTG GTG G TG ACG G TAAAAT G AAA G
AT CTC AGTCC AAGAT G GT
ATTTCTACTACCTAG GAACTG G G CCAGAAG CTG GACTTCCCTATG GTG CTAACAAAGACG G CAT
CATATG G GTTG CAACTG
AGG GAG CCTTG AATACACCAAAAGATCACATTGG CACC CG CAATCCTG CTAACAATG CTG CAATCGTG
CTACAACTTCCTC
AAG GAACAACATTG CCAAAAGG CTTCTACGCAGAAG G GAG CAG AG G CGG CAGTCAAG
CCTCTTCTCGTTCCTCATCACGT
AGTCG CAACAGTTCAAG AAATTCAACTCCAG G CAG CAG TAG G GG AATTTCTCCTG CTAGAATG
GCTGG CAATG GCG G TG A
TG CT G CT CTTG CTTTG CT G CT G CTTGACAG ATTG AACCA G CTT G AG A G
CAAAATGTCTGG TAAAG G CCAA CAACAA CAA G G
CCAAACTGTCACTAAG AAATCTG CTG CT G AG G CTTCTAAG AAG CCTCG G CAAAAACGTACTG CC
ACTAAA G CATAC AAT GT
AACACAAG CTTTC G G CAG ACGTG GTCCAG AA CAAACC CAAG G AAATTTTG GGGACCAG
GAACTAATCAG ACAAG GAACT
GATTACAAACATTG G CCG CAAATTG CACAATTTG CCCCCAGCG CTTCAG CGTTCTTCG GAATGTCG CG
CATTG G CATG G AA
GTCACACCTTCG G GAACGTG GTTG AC CTACA CAG GTG CCATCAAATTG GATG
ACAAAGATCCAAATTTCAAAGATCAAGTC
ATTTTG CTGAATAAG CATATTG AC G CATA CAAAAC ATTT CCACCAAC AG AG CCTAAAAAG G
ACAAAA AG AAG AAG G CTG A
TG AAACTCAAGCCTTACCG CA G AG AC AG AAG AAACAG CAAACTGTGACTCTTCTTCCTG CT G CA G
ATTTG G AT G ATTTCTC

CAAACAATTG CAACAATCCATG AG CAGTG CTGACTCAACTCAG G CCTAAACTCATG CAGACCACACAAG G
CAGATG G G CT
ATATAAACGTTTTCGCTTTTCCGTTTACGATATATAGTCTACTCTTGTGCAGAATGAATTCTCGTAACTACATAGCACA
AGTA
GATGTAGTTAACTTTAATCTCACATAG CAATCTTTAAT CAGTGTGTAACATTAG G GAG G ACTTGAAAGAG
CCACCACATTTT
CACCGAGG CCACGCGGAGTACGATCGAGTGTACAGTGAACAATGCTAG G GAG AG CTG CCTATATG GAAGAG
CCCTAATG
TGTAAAATTAATTTTAGTAGTGCTATCCCCATGTGATTTTAATAGC
SEQ ID NO: 27 >QPJ72086.1. S-protein surface glycoprotein M FVFLVLLPLVSIQCVN LTTRTQLPPAYTNSFTRGVYYPDKVF RSSVLHSTQDLFLPFFSNVTWF HAI
HVSGTNGTKRF DNPVLP F
NDGVYFASTEKSNIIRGWIFGTTLDSKTQSLLIVNNATNVVIKVCEFQFCN DPF LGVYYHKNN KSCMESEF
RVYSSANNCTF EYVS
QPFLM DLEG KQGN F KN LREFVF KN IDGYF KIYSK HIP I N LVRDLPQG FSALE P LVDLP IG I
NITRFQTLLALHRSYLTPGDSSSGWT
AGAAAYYVGYLQP RTF LLKYN ENGTITDAVDCALDP LSETKCTL KSFTVEKG IYQTSNF
RVQPTESIVRFPN ITN LCP FG EVF NATR
FASVYAWN RKRISNCVADYSVLYNSASFSTF KCYGVSPTKLNDLCFINVYADSFVIRG
DEVRQIAPGQTGKIADYNYKLPDDFTG
CVIAWNSN NLDSKVGG NYNYRYRLFRKSNLKPF ERDISTEIYQAGSTPCNGVEGFNCYFPLQSYG
FQPINGVGYQPYRVVVLSF
ELLHAPATVCG PKKSTNLVKNKCVNF N F NG LTGTGVLTESN KKFL PFQQFG
RDIADTTDAVRDPQTLEILDITPCSFGGVSVITPG
TNTSNQVAVLYQGVNCTEVPVAI HADQLTPTWRVYSTGSNVFQTRAGCLI GAE HVN NSYECD IP IGAG
ICASYQTQTNSP RRAR
SVASQSI lAYTMSLGAENSVAYSNNSIA1 PTN FTISVTTEI LPVS MTKTSVDCTM YICG DSTECSN
LLLQYGSFCTQL NRALTG !AVE
QD KNTQEVFAQVKQIYKTP PI KDFGG F N FSQI LP DPSKPSKRSF I E DL LF NKVTLADAG Fl KQYG DC LGD IAARDLICAQKFNG LTV
LP P LLTDE M IAQYTSALLAGTITSGWTFGAGAALQIPFAMQMAYRF NG IGVTQNVLYENQK LIANQF
NSAIG KIQDSLSSTASAL
G KLQDVVNQNAQALNTLVKQLSSNFGAISSVLN DI LSRLDKVEAEVQIDRLITGRLQSLQTYVTQQLI
RAAEIRASANLAATKMSE
CVLGQSKRVDFCG KGYHLMSFPQSAPHGVVF LHVTYVPAQEKNFTTAPAICHDG
KAHFPREGVFVSNGTHWFVTQRNFYEPQ

IDRLN EVAKNLNESLIDL

DDSEPVLKGVKLHYT
SEQ ID NO: 28 >nucleocapsid phosphoprotein [Severe acute respiratory syndrome coronavirus 2]
(Accession No: QIA98561) MSDNG PQNQR NAP RITFGG PSDSTGSNQNG ERSGARSKURPQG LPN NTASWFTALTQHG KEDLKF
PRGQGVP I NTNSSP
DDQIGYYRRATRRIRGGDGKM KDLSPRWYFYYLGTG PEAG LPYGANKDG I IWVATEGALNTPKDHIGTRN
PAN NAAIVLQLP
QGTTLPKGFYAEGSRGGSQASSRSSSRSRNSSRNSTPGSSRGTSPARMAGNGGDAALALLLLDRLNQLESKMSGKGQQQ
QG
QTVTKKSAAEASKKP RQKRTATKAYNVTQAFGRRG P EQTQGN FG DQE LI RQGTDYKHW
PQIAQFAPSASAF FGMSRIGM EV
TPSGTWLTYTGAIKLDDKDPN FKDQVI LLN KHIDAYKTF
PPTEPKKDKKKKADETQALPQRQKKQQTVTLLPAADLDDFSKQLQ
QSM SSA DSTQA
SEQ ID NO: 29 >membrane glycoprotein [Severe acute respiratory syndrome coronavirus 2]
(Accession No: 0IA98557) MADSNGTITVEELKKLLEQWNLVIG F LF LTWICLLQFAYAN RN RF LYI I KLI FLWLLWPVT
LACFVLAAVYRI NW ITGG IAIAMACL

HHLGRCDIKDLPKEITVATSRT
LSYYKLGASQRVAGD SG FAAYSRYRIG NY KLNTD HSSSSD N IALLVQ

Claims (64)

PCT/EP2021/058974
1. A SARS-CoV-2 vaccine comprising a beta-propiolactone-inactivated SARS-CoV-2 particle, wherein the vaccine is capable of generating neutralizing antibodies against native SARS-CoV-2 particles in a human subject.
2. A SARS-CoV-2 vaccine according to claim 1, wherein a native surface conformation of the SARS-CoV-2 particle is preserved in the vaccine.
3. A SARS-CoV-2 vaccine according to claim 1 or 2, wherein viral RNA in the inactivated SARS-CoV-2 particle is replication-deficient, preferably wherein viral RNA in the inactivated SARS-CoV-2 particle (i) is alkylated and/or acylated (ii) comprises one or more modified purine (preferably guanine) residues and/or strand breaks and/or (iii) is cross-linked with one or more viral proteins.
4. A SARS-CoV-2 vaccine according to any preceding claim, wherein the SARS-CoV-2 particle is beta-propiolactone-inactivated at a concentration of 300 to 700ppm, more preferably 500ppm and inactivated for about 1 to 48h, preferably 20 to 28h, most preferred 24 hours 2 hours (such as also 1 hour or 0.5 hour) at 2 C to 8 C, followed optionally by a hydrolyzation for 2.5 hours 0.5 hours at 35 C to 39 C, preferably around 37 C.
5. A SARS-CoV-2 vaccine according to any preceding claim, further comprising an ultraviolet (UV)-inactivated SARS-CoV-2 particle.
6. A SARS-CoV-2 vaccine according to any preceding claim, wherein surface proteins in the inactivated SARS-CoV-2 particle comprise reduced modifications compared to viral RNA in the inactivated SARS-CoV-2 particle, preferably wherein surface proteins comprise a reduced proportion of modified residues compared to viral RNA in the inactivated SARS-CoV-2 particle;
said modifications being with respect to a native SARS-CoV-2 particles, preferably wherein said modifications comprise alkylated and/or acylated nucleotide or amino acid residues.
7. A SARS-CoV-2 vaccine according to any preceding claim, wherein the inactivated SARS-CoV-2 particle comprises a native conformation of (i) spike (S) protein; (ii) nucleocapsid (N) protein;
(iii) membrane (M) glycoprotein; and/or (iv) envelope (E) protein; preferably wherein the inactivated SARS-CoV-2 particle comprises a native conformation spike (S) protein.
8. A SARS-CoV-2 vaccine according to any preceding claim, wherein the inactivated SARS -CoV-2 particle comprises one or more beta-propiolactone-modified cysteine, methionine and/or histidine residues.
9. A SARS-CoV-2 vaccine according to any preceding claim, wherein an inactivated SARS-CoV-2 particle comprises fewer than 200, 100, 50, 30, 20, 15, 10, 9, 8, 7 or 6 beta-propiolactone-modified amino acid residues; preferably wherein a spike (S) protein of the inactivated SARS-CoV-2 particle comprises fewer than 100, 50, 30, 20, 15, 10, 9, 8, 7 or 6 beta-propiolactone-modified amino acid residues; more preferably wherein the inactivated SARS-CoV-2 particle or spike protein thereof comprises 15 or fewer beta-propiolactone-modified amino acid residues;
most preferably whcrcin the inactivated SARS-CoV-2 particle or spike protein thereof comprises 1 to 100, 2 to 50, 3 to 30, 5 to 20 or about 15 beta-propiolactone-modified amino acid residues.
10. A SARS-CoV-2 vaccine according to any preceding claim, wherein fewer than 20%, 15%, 10%, 5% or 4% of SARS-CoV-2 polypeptidcs in the particle are beta-propiolactonc-modified;
preferably wherein 0.1 to 10%, more preferably 1 to 5%, more preferably 2 to 8% or about 3-6%
of SARS-CoV-2 polypeptides in the particle, comprise at least one beta-propiolactone modification; preferably as detected in the vaccine by mass spectroscopy, optionally following enzymatic digestion with trypsin, chymotrypsin and/or PNGase F or acid hydrolysis.
11. A SARS-CoV-2 vaccine according to any preceding claim, wherein:
(i) a spike (S) protein of the inactivated SARS-CoV-2 particle comprises a beta-propiolactone modification at one or more of the following residues: 49, 146, 166, 177, 207, 245, 379, 432, 519, 625, 1029, 1032, 1058, 1083, 1088, 1101, 1159 and/or 1271; preferably H49, H146, C166, M177, H207, H245, C432, H519, H625, M1029, H1058, H1083, H1088, H1101, H1159 and/or H1271; or H207, H245, C379, M1029 and/or C1032, e.g. in SEQ ID NO: 3, or a corresponding position in SEQ TD NO: 19, 21, 23, 25 or 27; and/or (ii) a membrane (M) glycoprotein of the inactivated SARS-CoV-2 particle comprises a beta-propiolactone modification at one or more of the following residues: 125, 154, 155, 159 and/or 210; preferably H154, H155, C159 and/or H210, e.g. in SEQ ID NO: 29;
(iii) a nucleocapsid (N) protein of the inactivated SARS-CoV-2 particle comprises a beta-propiolactone modification at M234, e.g. in SEQ ID NO: 28.
12. A SARS-CoV-2 vaccine according to any preceding claim, wherein fewer than 30%, 20%, 10%, 5%, 3% or 1% of one or more of the following residues, preferably of at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or all of the following residues, in the inactivated SARS-CoV-2 particles are beta-propiolactone modified:
(i) in the spike (S) protein, residues 49, 146, 166, 177, 207, 245, 379, 432, 519, 625, 1029, 1032, 1058, 1083, 1088, 1101, 1159 and/or 1271; preferably H49, H146, C166, M177, H207, H245, C432, H519, H625, M1029, H1058, H1083, H1088, H1101, H1159 and/or H1271; or H207, H245, C379, M1029 and/or C1032; e.g. in SEQ ID NO: 3, or a corresponding position in SEQ
ID NO: 19, 21, 23, 25 or 27; and/or (ii) in the membrane (M) glycoprotein, residues 125, 154, 155, 159 and/or 210; preferably H154, H155, C159 and/or H210; e.g. in SEQ ID
NO: 29; and/or (iii) M234 of the nucleocapsid (N) protein, e.g. in SEQ ID NO: 28.
13. A SARS-CoV-2 vaccine according to any preceding claim, wherein thc proportion of beta-propiolactone-modified residues at each of the following positions in the inactivated SARS-CoV-2 particles is:
(i) in the spike (S) protein (e.g. of SEQ ID NO: 3, or a corresponding position in SEQ ID NO:
19, 21, 23, 25 or 27):
(a) residues H49, H146, C166, H207, H519, M1029, H1083, H1088, H1101, H1159 and/or H1271: less than 20%, preferably 0.01 to 10%, more preferably 0.1 to 5%;
and/or (b) residues M177, C432, H625: less than 30%, preferably 0.1 to 20%, more preferably 1 to 10%; and/or (c) residues H245, H1058: less than 30%, preferably 0.1 to 20%, more preferably 5 to 15%;
(ii) in the membrane (M) glycoprotein (e.g. of SEQ ID NO: 29):
(f) H154: less than 5%, less than 1% or less than 0.1%; and/or (g) H155: less than 10%, preferably 0.1 to 5%; and/or (h) C159: less than 5%, less than 1% or less than 0.1%; and/or (i) H210: less than 20%, preferably 0.1 to 10%; and/or (iii) in the nucleocapsid (N) protein (e.g. of SEQ ID NO: 28):
(j) M234: less than 90%; less than 10% or less than 0.1%.
14.
A SARS-CoV-2 vaccine according to any preceding claim, wherein infectivity of mammalian cells by the inactivated SARS-CoV-2 particle is reduced by at least 99%, 99.99% or 99.9999%
compared a native SARS-CoV-2 particle, or wherein infectivity of mammalian cells by the inactivated A SARS-CoV-2 particle is undetectable.
15. A SARS-CoV-2 vaccine according to any preceding claim, further comprising one or more pharmaceutically acceptable excipients, such as e.g., human serum albumin (HSA).
16. A SARS-CoV-2 vaccine according to any preceding claim, further comprising an adjuvant.
17. A SARS-CoV-2 vaccine according to claim 16, wherein the adjuvant comprises aluminium hydroxide or aluminium phosphate.
18. A SARS-CoV-2 vaccine according to claim 17, wherein aluminium hydroxide or aluminium phosphate is the only adjuvant in the vaccine.
19. A SARS-CoV-2 vaccine according to claim 16 or 17, wherein the adjuvant comprises or further comprises a Thl response-directing adjuvant.
20. A SARS-CoV-2 vaccine according to claim 19, wherein the Thl response-directing adjuvant comprises 3-0-desacy1-4'-monophosphoryl lipid A (MPL), saponin QS-21, a CpG-containing oligodeoxynucleotide (CpG ODN), squalene, DL-a-tocopherol, a cationic peptide, a deoxyinosine-containing immunostimulatory oligodeoxynucleic acid molecule (I-ODN) and/or imiquimod.
21. A SARS-CoV-2 vaccine according to claim 16, wherein the adjuvant comprises:
(i) a liposomal preparation comprising 3-0-desacy1-4'-monophosphoryl lipid A
(MPL) and saponin QS-21, preferably Adjuvant System 01;
(ii) a CpG ODN comprising the sequence 5' TGACTGTGAACGTTCGAGATGA 3' (SEQ ID
NO:4), preferably CpG 1018;
(iii) squalene, DL-a-tocopherol and polysorbate 80 (preferably Adjuvant System 03);
(iv) an oil-in-water emulsion comprising squalene, Tween 80 and Span 85, preferably MF59;
(v) a peptide of sequence KLKLSKLK (SEQ ID NO: 5) and oligo-d(IC)13 (SEQ TD
NO: 6), preferably IC31; or (vi) an aluminium salt and optionally a Thl-directing adjuvant.
22. The SARS-CoV-2 vaccine according to any preceding claim, wherein the vaccine is able to seroconvert a subject that is administered the SARS-CoV-2 vaccine with at least a 70%
probability.
23. The SARS-CoV-2 vaccine according to claim 22, wherein the SARS-CoV-2 vaccine is able to seroconvert the subject that is administered the SARS-CoV-2 vaccine with at least an 80%, 85%, 90%, or 95% probability.
24.
The SARS-CoV-2 vaccine according to any one of the preceding claims, wherein the SARS-CoV-2 particle comprises an RNA sequence (and/or fragments thereof, optionally comprising modified (preferably alkylated or acylated) nucleotide residues) corresponding to a DNA
sequence (i) as defined by SEQ ID NO: 9; or (ii) having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID NO: 9; preferably wherein a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence is able to pack a virulent SARS-CoV-2.
25. The SARS-CoV-2 vaccine according to any one of the preceding claims, wherein the said vaccine comprises an additional SARS-CoV-2 particle that comprises an RNA sequence (and/or fragments thereof, optionally comprising modified (preferably alkylated or acylated) nucleotide residues) corresponding to a DNA sequence (i) as defined by SEQ ID NO: 18; or (ii) having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID
NO: 18; preferably wherein a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence is able to pack a virulent SARS-CoV-2.
26. The SARS-CoV-2 vaccine according to any one of the preceding claims, wherein the said vaccine comprises an additional SARS-CoV-2 particle that comprises an RNA sequence (and/or fragments thereof, optionally comprising modified (preferably alkylated or acylated) nucleotide residues) corresponding to a DNA sequence (i) as defined by SEQ ID NO: 22; or (ii) having at least 80%, at least 85%, at least 90%, at least 95% or at least 99% sequence identity to SEQ ID
NO: 22; preferably wherein a native (non-inactivated) SARS-CoV-2 particle comprising the RNA sequence is able to pack a virulent SARS-CoV-2.
27. The SARS-CoV-2 vaccine according to any preceding claim, wherein the vaccine is obtained or obtainable from Vero cells.
28. The SARS-CoV-2 vaccine according to any preceding claim, wherein, upon administration to a human subject, the vaccine (i) does not induce antibody-dependent enhancement (ADE) of SARS-CoV-2-associated disease (COVID-19); and/or (ii) does not induce immunopathology in the subject.
29. A method of preventing or treating SARS-CoV-2 infection and/or SARS-CoV-2-associated disease (COVID-19) in a human subject in need thereof, comprising administering a prophylactically or therapeutically effective amount of the SARS-CoV-2 vaccine of any preceding claim to the subject.
30. The method according to claim 29, further comprising administering a second dose of a prophylactically or therapeutically effective amount of the SARS-CoV-2 vaccine, preferably wherein the second dose of the vaccine is the same formulation as the first.
31. The method according to claim 29 or 30, wherein said prophylactically or therapeutically effective amount of the SARS-CoV-2 vaccine per dose is defined as about 1 to 100 AU/dose, preferably between about 2 to 75 AU/dose, preferably between about 3 and 60 AU/dose, more preferably between about 3 and 55 AU/dose, more preferably between about 3 and 53 AU/dose, as assessed by ELISA, even more preferably between about 3 and 40 AU/dose, more preferably about 10 to 60 AU/dose, 20 to 50 AU/dose, 25 to 45 AU/dose or 30 to 40 AU/dose, such as e.g.
35 AU/dose or 40 AU/dose.
32. The method according to claim 29 or 30, wherein said prophylactically or therapeutically effective amount per dose of the SARS-CoV-2 vaccine is defined as about 0.05 to 50 ng total protein, about 0.1 to 25 pg, about 0.25 to 12.5 ng, preferably about 0.5 to 5 ng total protein, more preferably at least 2.5 lig total protein, at least 3.5 pig total protein or at least 2.5 pg total protein, even more preferably 2.5 ng to 25 lig, 3.5 ng to 10 pg or 4 ng to 6 ng total protein/dose, most preferably about 5 pg total protein/dose, e.g as measured by (n)BCA.
33. The method according to claim 29 or 30, wherein said prophylactically or therapeutically effective amount per dose of the SARS-CoV-2 vaccine is defined as about 0.025 to 25 jig S-protein, about 0.05 to 12.5 ng, about 0.125 to 6.25 ng, preferably about 0.25 to 2.5 ng S-protein, as measured by ELISA.
34. The method according to claim 30, wherein the second dose of the SARS-CoV-2 vaccine is administered about 7 days, about 14 days, about 21 days, or about 28 days after a first dose of the SARS-CoV-2 vaccine, preferably wherein the second dose of the vaccine is the same formulation as the first.
35. The method according to any one of claims 28 to 34, wherein the administering results in production of SARS-CoV-2 neutralizing antibodies.
36. A method of producing a SARS-CoV-2 vaccine, comprising:
(a) producing native SARS-CoV-2 particles;
(b) inactivating the native SARS-CoV-2 particles to obtain inactivated SARS-CoV-2 particles;
(c) incorporating the inactivated SARS-CoV-2 particles in a vaccine composition;
wherein a native surface conformation of the SARS-CoV-2 particle is preserved in the inactivation step, such that the vaccine is capable of generating neutralizing antibodies against native SARS-CoV-2 particles in a human subject.
37. The method according to claim 36, wherein the vaccine composition comprises aluminium hydroxide.
38. The method according to claim 37, wherein the SARS-CoV-2 vaccine comprising aluminium hydroxide contains less than 1.25 ppb Cu.
39. The method according to any of claims 36 to 38, wherein the inactivation step preferentially targets viral RNA in the SARS-CoV-2 particle.
40. The method according to claim 36 or 39, wherein the inactivation step comprises (i) alkylating and/or acylating viral RNA (ii) modifying purine (preferably guanine) residues or introducing strand breaks into viral RNA and/or (iii) cross-linking viral RNA with one or more viral proteins.
41. The method according to any one of claims 36, 39 or 40, wherein the inactivation step comprises treating the native SARS-CoV-2 particles with beta-propiolactone.
42. The method according to claim 41, wherein the concentration of beta-propiolactone in the inactivation step is 0.01 to 1% by weight, preferably 0.05 to 0.5% by weight, more preferably about 0.1% by weight.
43. The method according to claim 41 or 42, wherein the native SARS-CoV-2 particles are contacted with beta-propiolactone for at least 5 hours, at least 10 hours, at least 24 hour or at least 4 days.
44. The method according to any of claims 36 or 39 to 43, wherein the inactivation step is performed at about 0 C to about 25 C, preferably about 4 C or about 22 C.
45. The method according to any of claims 36 or 39 to 44, wherein the inactivation step comprises treating the native SARS-CoV-2 particles with ultraviolet (UV) light.
46. The method according to any one of claims 36 or 39 to 45, wherein step (a) comprises one or more of the following steps:
(i) passaging a SARS-CoV-2 on Vero cells, thereby producing a culture medium comprising the SARS-CoV-2;
(ii) harvesting the culture medium of (i);
(iii) precipitating the harvested culture medium of (ii), thereby producing native SARS-CoV-2 particles in a supernatant.
47. The method according to claim 46, further comprising concentrating the culture medium of (ii) prior to step (iii).
48. The method according to claim 46 or 47, wherein the precipitating of (iii) comprises contacting the culture medium of (ii) with protamine sulfate or benzonase.
49. The method according to any one of claims 36 or 39 to 48, further comprising dialyzing the inactivated SARS-CoV-2 particles, thereby producing a dialyzed SARS-CoV-2.
50. The method according to claim 49, further comprising filtering the dialyzed SARS-CoV-2.
51. The method according to any one of claims 36 or 39 to 50, wherein the inactivation step comprises contacting a liquid composition comprising native SARS-CoV-2 particles with a chemical viral inactivating agent in a container, mixing the chemical viral inactivating agent and the liquid composition comprising SARS-CoV-2 particles under conditions of laminar flow but not turbulent flow, and incubating the chemical viral inactivating agcnt and the liquid composition comprising SARS-CoV-2 particles for a time sufficient to inactivate the viral particles.
52. The method according to claim 51, wherein the inactivation step is performed in a flexible bioreactor bag.
53. The method according to claim 51 or 52, wherein the inactivation step comprises five or less container inversions during the period of inactivation.
54. The method according to any one of claims 51 to 53, wherein the mixing of the chemical viral inactivating agent and the composition comprising native SARS-CoV-2 particles comprises subjecting the container to rocking, rotation, orbital shaking, or oscillation for not more than 10 minutes at not more than 10 rpm during the period of incubation.
55. The method according to any one of claims 36 or 39 to 54, further comprising purifying the inactivated SARS-CoV-2 particles by one or more methods selected from (i) batch chromatography and/or (ii) sucrose density gradient centrifugation.
56. The method according to any one of claims 36 or 39 to 55, wherein step (c) comprises combining the inactivated SARS-CoV-2 particles with an adjuvant.
57. The method according to claim 56, wherein the adjuvant comprises a Thl response-directing adjuvant.
58. The method according to claim 56 or 57, wherein the adjuvant comprises 3-0-desacyl-4'-monophosphoryl lipid A (MPL), saponin QS-21. a CpG-containing oligodeoxynucleotide (CpG
ODN), squalene, DL-a-tocopherol and/or imiquimod.
59. A SARS-CoV-2 vaccine obtained or obtainable by the method of any one of claims 36 or 39 to 58.
60. Use of a SARS-CoV-2 vaccine of any one of claims 1 to 28 or 59 for the treatment or prevention of a SARS-CoV-2 infection in a subject.
61. A pharmaceutical composition for use in the prevention or treatment of a SARS-CoV-2 infection in a subject, wherein said pharmaceutical composition is the inactivated SARS-CoV-2 vaccine as defined in any one of claims 1 to 28 or 59, optionally in combination with one or more pharmaceutically acceptable excipients and/or adjuvants.
62. The SARS-CoV-2 vaccine as defined in any one of claims 1 to 28 or 59 for use as a medicament.
63. A vaccine, method, use or pharmaceutical composition according to any preceding claim, wherein the subject is (i) an elderly subject, preferably a subject over 65, over 70 or over 80 years of age; (ii) an immunocompromised subject; or (iii) a pregnant subject_
64. A vaccine, method, use or pharmaceutical composition according to any preceding claim, for use in prevention or treatment of a SARS-CoV-2 infection without induction of (i) antibody-dependent enhancement (ADE) of SARS-CoV-2-associated disease (COVID-19);
and/or (ii) immunopathology in the subject.
CA3168784A 2020-04-06 2021-04-06 Inactivated sars-cov-2 virus vaccine Pending CA3168784A1 (en)

Applications Claiming Priority (13)

Application Number Priority Date Filing Date Title
EP20168324.0 2020-03-01
EP20168324 2020-04-06
EP20202118 2020-10-15
EP20202118.4 2020-10-15
EP20211853 2020-12-04
EP20211853.5 2020-12-04
EP21154647.8 2021-02-01
EP21154647 2021-02-01
USPCT/US21/20313 2021-03-01
PCT/US2021/020313 WO2021178318A1 (en) 2020-03-01 2021-03-01 Coronavirus vaccines comprising a tlr9 agonist
EP21160913.6 2021-03-05
EP21160913 2021-03-05
PCT/EP2021/058974 WO2021204825A2 (en) 2020-04-06 2021-04-06 INACTIVATED SARS-CoV-2 VIRUS VACCINE

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