EP4146242A1 - Peptides pour la prévention ou le traitement d'infections virales - Google Patents

Peptides pour la prévention ou le traitement d'infections virales

Info

Publication number
EP4146242A1
EP4146242A1 EP21722499.7A EP21722499A EP4146242A1 EP 4146242 A1 EP4146242 A1 EP 4146242A1 EP 21722499 A EP21722499 A EP 21722499A EP 4146242 A1 EP4146242 A1 EP 4146242A1
Authority
EP
European Patent Office
Prior art keywords
seq
peptide
peptides
amino acid
sars
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP21722499.7A
Other languages
German (de)
English (en)
Inventor
Philippe KAROYAN
Olivier Lequin
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Centre National de la Recherche Scientifique CNRS
Ecole Normale Superieure
Sorbonne Universite
Original Assignee
Centre National de la Recherche Scientifique CNRS
Ecole Normale Superieure
Sorbonne Universite
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Centre National de la Recherche Scientifique CNRS, Ecole Normale Superieure, Sorbonne Universite filed Critical Centre National de la Recherche Scientifique CNRS
Publication of EP4146242A1 publication Critical patent/EP4146242A1/fr
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/485—Exopeptidases (3.4.11-3.4.19)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/17—Metallocarboxypeptidases (3.4.17)
    • C12Y304/17023—Angiotensin-converting enzyme 2 (3.4.17.23)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • the invention pertains to a new group of peptides that mimic an a-helix structure of the human Angiotensin Converting Enzyme 2 (hACE2) to bind the Spike protein (protein S) of viruses, in particular of coronaviruses.
  • hACE2 human Angiotensin Converting Enzyme 2
  • proteins S Spike protein
  • coronavirus disease 2019 2019 (COVID-19), caused by the severe acute respiratory syndrome - coronavims 2 (SARS-CoV-2) has emerged as a pandemic, claiming more than 117 000 deaths and around 1,8 million confirmed cases world- wide between December 2019 and April 2020.
  • SARS-CoV-2 discovery and identification the energy deployed by the scientific community has made it possible to generate an extraordinary amount of data, both in terms of quality and quantity.
  • clinically approved vaccines or drugs are lacking. Indeed, no specific drugs targeting this new virus are available, but many clinical trials have been engaged with non-specific treatments. Many vaccine approaches are also currently under investigation at a pandemic speed. But referring to coronaviruses specialists, SARS-CoV-2 vaccine might be produced within 12 to 18 months. Indeed, vaccine development is a lengthy and expensive process. Attrition is high, and it typically takes multiple candidates and many years to produce an approved vaccine.
  • peptides are widely recognized as promising therapeutic agents for the treatment of various conditions such as cancer, and metabolic, infectious or cardiovascular diseases. Across the United States, Europe, and Japan, to date more than 60 peptide drugs have reached the market and more than 150 are actually under clinical development. Special advantages that peptides show over other drugs include being highly versatile, target- specific, less toxic, and able to act on a wide variety of targets which are directly responsible for greater success rate than small molecules (approval rate of around 20% versus 10%). In this context, the Inventors have developed an innovative approach using peptides to mimic a receptor targeted by the virus in order to block its infectivity, mainly in a preventive manner to stop the pandemic.
  • S protein virus cell-surface Spike protein
  • TMPRSS2 cellular Transmembrane Protease Serine 2
  • SI contains the receptor binding domain (RBD), which directly binds to the peptidase domain (PD) of angiotensin-converting enzyme 2 (ACE2), whereas S2 is responsible for membrane fusion.
  • RBD receptor binding domain
  • PD peptidase domain
  • S2 is responsible for membrane fusion.
  • S 1 binds to the host receptor ACE2
  • another cleavage site on S2 is exposed and is cleaved by host proteases, a process that is critical for viral infection.
  • blocking the virus-hACE2 interaction appears as a relevant therapeutic approach of coronavirus, and particularly for prophylaxis.
  • the peptides of the present invention have many advantages. They were designed and optimized for binding, high helical content and low antigenicity, to avoid triggering a neutralizing immune response that would compromise the peptide therapeutic potential. They mimic hACE2, which is an extracellular target, easier to address that an intracellular one. Their bio-distribution can be restricted to the upper airways (oral cavity, ...) in a prophylactic approach and they will be degraded in the digestive tracks without any toxic residues. In case of blood stream access, they will have a short half-life and thus, they will not be toxic for humans.
  • the intrinsic limitations for peptides generally include metabolic instability, which is the inability to withstand 600 proteases in the human body, and restriction to the parenteral route of administration.
  • peptides of the invention can overcome these challenges by incorporating additional entities, such as non-natural amino acids, to improve the metabolic stability, or other chemical entities, such as polyethylene glycols, to enhance membrane transportation. Nevertheless, this metabolic stability issue is not crucial in a prophylactic approach. Indeed, a peptide formulated for oral administration and release such as sublingual tablets for example, using only natural amino acids will be advantageously degraded in natural amino acids to avoid any risk of toxicity after metabolism of degradation. Moreover, to avoid any other toxicity issue, the peptides of the invention are designed de novo from a human protein, an endogenous target of the SARSCoV-2, but also a target of others coronavims.
  • the invention thus relates to a peptide comprising or consisting in an amino acid sequence of SEQ ID NO: 1:
  • S-X-X-X-X-Q-X-X-T-F-X-D-K-X-X-H-E-X-E-[D/P/mA]-X-X-Y-Q-X-X-L (SEQ ID NO: 1), wherein X is any amino acid, and mA is a N-methyl-alanine, or a pharmaceutically acceptable salt thereof.
  • the peptide according to the invention which may be isolated, recombinant or synthetic, preferably synthetic, comprises or consists of an amino acid sequence.
  • This sequence defines a pharmacologically active peptide which mimics part of an a-helix structure from hACE2 that binds the Spike protein of viruses. This property can be readily verified by techniques known to those skilled in the art such as those described in the examples of the present application.
  • the invention encompasses a peptide comprising or consisting of natural amino acids (20 gene-encoded amino acids in L- and/or D-configuration) linked via a peptide bond, as well as mimetics of such peptides wherein some amino acids and/or peptide bonds have been replaced by functional analogues.
  • Such functional analogues include all known amino acids other than the 20 gene- encoded amino acids (or canonical amino acids).
  • a non-limitative list of non- coded amino acids (or non-canonical amino acids) is provided in Table 1A of US 2008/0234183.
  • the invention also encompasses modified peptides derived from the above peptides by introduction of any modification into one or more amino acid residues, peptide bonds, N-and/or C-terminal ends of the peptide, as long as their property of binding to hACE2 is maintained in the modified peptide.
  • modifications which are introduced into the peptide by conventional methods known to those skilled in the art include, in a non-limiting manner: the substitution of a natural amino acid with a non-proteinogenic amino acid (D amino acids or amino acid analogs); the modification of the peptide bond, in particular with a bond of the retro or retro-inverso type or a bond different from the peptide bond; the cyclization; the modification of the end(s) of the peptide, in particular a N-acetamido protection at the N-ter extremity and/or a C-carboxamide protection at C-ter extremity, and the addition of a chemical group to the side chain or the end(s) of the peptide, in particular for coupling an agent of interest to the peptide of the invention.
  • compositions disclosed herein are included in the present invention.
  • an acid salt of a compound containing an amine or other basic groups can be obtained by reacting the compound with a suitable organic or inorganic acid, resulting in pharmaceutically acceptable anionic salt forms.
  • anionic salts include the acetate, benzenesulfonate, benzoate, bicarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, glyceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylsulfate, mucate, napsylate, nitrate, pamoate, pantothenate, phosphate/diphospate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulfate, tannate,
  • Salts of the compounds containing an acidic functional group can be prepared by reacting with a suitable base.
  • a suitable base which affords a pharmaceutically acceptable cation, which includes alkali metal salts (especially sodium and potassium), alkaline earth metal salts (especially calcium and magnesium), aluminum salts and ammonium salts, as well as salts made from physiologically acceptable organic bases such as trimethylamine, triethylamine, morpholine, pyridine, piperidine, picoline, dicyclohexylamine, N,N'-dibenzylethylenediamine, 2-hydroxyethylamine, bis-(2-hydroxyethyl)amine, tri-(2- hydroxyethyl)amine, procaine, dibenzylpiperidine, dehydroabietylamine, N,N'- bisdehydroabietylamine, glucamine, N-methylglucamine, collidine, quinine, quinoline, and basic amino acids such as lysine
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 2:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 3:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 4:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 5:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 6:
  • the peptide of the invention peptide comprises or consists in an amino acid sequence of SEQ ID NO: 7: S-X-X-X-X-Q-X-X-T-F-X-D-K-X-X-H-E-X-E-[D/P/mA]-X-X-Y-Q-X-X-L-X-X (SEQ ID NO: 7), wherein X is any amino acid, and mA is a N-methyl-alanine, or a pharmaceutically acceptable salt thereof.
  • the peptide of the invention peptide comprises or consists in an amino acid sequence of SEQ ID NO: 8:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 9: S - [T/L/A/V/I] - [EL/A] -E-X-Q-X-X-T-F-X-D-K-X-X-H-E-X-E- [D/PmA] -X-X- Y-Q-X-X-L- X-X (SEQ ID NO: 9), wherein X is any amino acid, and mA is a N-methyl-alanine, or a pharmaceutically acceptable salt thereof.
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 10:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 11:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 12:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 13:
  • the peptide of the invention comprises or consists in an amino acid sequence of SEQ ID NO: 14:
  • the peptide of the invention comprises or consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49
  • the peptide of the invention comprises or consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49
  • the peptide of the invention comprises or consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 40, SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 47, SEQ ID NO: 48, SEQ ID NO: 49
  • the peptide of the invention comprises or consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 66, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76 and SEQ ID NO: 79.
  • the peptide of the invention comprises or consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 15, SEQ ID NO: 17, SEQ ID NO: 20, SEQ ID NO: 55, SEQ ID NO: 56, SEQ ID NO: 57, SEQ ID NO: 59, SEQ ID NO: 60, SEQ ID NO: 66, SEQ ID NO: 74, SEQ ID NO: 75, SEQ ID NO: 76, SEQ ID NO: 79, SEQ ID NO: 152 and SEQ ID NO: 153.
  • the peptide of the invention does not comprise or consist in an amino acid sequence of SEQ ID NO: 15.
  • the peptide of the invention does not comprise or consist in an amino acid sequence of SEQ ID NO: 67. In an embodiment, the peptide is:
  • Nter-acetamido and Cter-carboxamide protected peptide Peptides consisting of SEQ ID NO: 80 to 145 are Cter-carboxamide protected. Peptide consisting of SEQ ID NO: 123 is Nter-acetamido and Cter-carboxamide protected.
  • the peptide of the invention consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 100,
  • SEQ ID NO: 140 SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, and SEQ ID NO: 145.
  • the peptide of the invention consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 80, SEQ ID NO: 81, SEQ ID NO: 82, SEQ ID NO: 83, SEQ ID NO: 84, SEQ ID NO: 85, SEQ ID NO: 86, SEQ ID NO: 87, SEQ ID NO: 88, SEQ ID NO: 89, SEQ ID NO: 90, SEQ ID NO: 91, SEQ ID NO: 92, SEQ ID NO: 93, SEQ ID NO: 94, SEQ ID NO: 95, SEQ ID NO: 96, SEQ ID NO: 97, SEQ ID NO: 98, SEQ ID NO: 99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO: 103, SEQ ID NO: 104, SEQ ID NO: 105, SEQ ID NO: 106, SEQ ID NO: 107, SEQ ID NO: 108, SEQ ID NO: 100,
  • SEQ ID NO: 140 SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 150 and SEQ ID NO: 151.
  • the peptide of the invention consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 85, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 132, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142 and SEQ ID NO: 145.
  • the peptide of the invention consists in an amino acid sequence selected from the group consisting of: SEQ ID NO: 80, SEQ ID NO: 82, SEQ ID NO: 85, SEQ ID NO: 120, SEQ ID NO: 121, SEQ ID NO: 122, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 132, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 145, SEQ ID NO: 150 and SEQ ID NO: 151.
  • the peptide of the invention only contains canonical (or natural) amino acids.
  • the peptide of the invention contains at least one non-canonical (or unnatural) amino acid.
  • the size of the peptide of the invention exceeds 27 amino acids length.
  • the size of the peptide of the invention is from 27 to 50 amino acids length.
  • the size of the peptide of the invention is 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 or 50 amino acids length.
  • the peptide of the invention has a helical content of at least 30%, preferably at least 40%, more preferably 50%.
  • the peptide of the invention has an helical content of at least 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95%, preferably of at least 50%.
  • the helical content can be determined using techniques known to those skilled in the art, such as those described in the examples of the present application.
  • the helical content is calculated using the Agadir program (Munoz & Serrano, 1994, Nature Struct. Biol., 1:399-409).
  • the peptide of the invention is not or low immunogenic.
  • the immunogenicity can be evaluated using techniques known to those skilled in the art, such as those described in the examples of the present application.
  • the immunogenicity is evaluated using the method of Kolaskar & Tongaonkar (FEBS Lett. 1990, 276(1-2): 172-174).
  • the peptide of the invention is labeled (or tagged).
  • the peptide of the invention is a chimeric peptide.
  • the peptide of the invention may comprise one or more other peptide moieties including some which can favor the purification, detection, immobilization of the peptide, and/or which increase its affinity for the protein S, its bioavailability, its production in expression systems and/or its stability.
  • such moieties may be selected from a labeling moiety (such as a fluorescent protein (GFP and its derivatives, BFP and YFP)), a reporter moiety (such as an enzyme tag (luciferase, alkaline phosphatase, glutathione-S- transferase (GST), b-galactosidase), a binding moiety such as an epitope tag (polyHis6, FLAG, HA, myc.), a DNA-binding domain, a poly-lysine tag for immobilization onto a support, and a targeting moiety for addressing the chimeric peptide to a specific tissue compartment.
  • a labeling moiety such as a fluorescent protein (GFP and its derivatives, BFP and YFP)
  • a reporter moiety such as an enzyme tag (luciferase, alkaline phosphatase, glutathione-S- transferase (GST), b-galactosidase)
  • the peptide of the invention is labeled (or tagged) with an agent allowing its detection by diagnostic techniques or medical imaging.
  • the peptide of the invention is a multimer, in particular a homomultimer.
  • a homomultimer refers to a peptide according to the invention wherein the sequence corresponding to the a-helix is repeated at least two times.
  • the peptide of the invention is a homodimer or a homotrimer, preferably a homotrimer.
  • a homodimer or a homotrimer preferably a homotrimer.
  • the Inventors have previously shown that multimerization, in particular homotrimerization, can improve potency of therapeutic peptides (Denefle el ah, J. Med. Chem. 2019, 62:7656-7668).
  • the percentage of inhibition of SARS-CoV-2 replication on Vero-E6 cells by the peptide of the invention at 10 mM is at least 50%, preferably 70%, more preferably 90
  • the percentage of inhibition of SARS-CoV-2 replication on Vero-E6 cells by the peptide of the invention at 10 pM is at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99%.
  • the peptide of the invention has an IC50 determined on Calu-3 cells inferior to 100 nM, preferably inferior to 70 nM. In an embodiment, the peptide of the invention has an IC50 determined on Calu-3 cells inferior to 100 nM, 90, nM, 80 nM, 70 nM, 60 nM or 50 nM.
  • the percentage of inhibition of SARS-CoV-2 replication on Vero-E6 cells and the IC50 determined on Calu-3 cells can be determined by techniques that are well known and commonly used by one skilled in the art, in particular as described in the present examples. All the embodiments and features given above for the peptide of the invention apply mutatis mutandis to the other aspects of the invention described below which involve said peptide.
  • the invention relates to the peptide as defined above for use as a medicament.
  • the present invention also relates to a method of prevention and/or treatment in a subject in need thereof comprising administering to said subject an effective amount of the peptide as defined above.
  • the present invention also relates to the use of the peptide as defined above in the manufacture of a medicament.
  • the peptide of the invention can be administered to the subject in conjunction with an acceptable pharmaceutical carrier as part of a pharmaceutical composition.
  • Formulation of a composition according to the invention can vary, for example in order to obtain a delayed effect or according to the route of administration selected.
  • the composition comprising the peptide is in the form of a solution, a syrup, a tablet, a pill, an eye-wash, a powder, a spray, a capsule, a gum, a pastille, a lipstick or an emulsion.
  • Suitable pharmaceutical carriers may contain inert ingredients which do not interact with the peptide.
  • Standard pharmaceutical formulation techniques can be employed, such as those described in Remington's Pharmaceutical Sciences, Mack Publishing Company, Easton, PA.
  • Suitable pharmaceutical carriers for parenteral administration include, for example, sterile water, physiological saline, bacteriostatic saline, phosphate-buffered saline, Hank's solution, Ringer's-lactate and the like.
  • a composition according to the invention contains a peptide as defined above in a concentration of at least 10 nM, preferably at least 100 nM, more preferably 1 mM.
  • the subject is an animal, preferably a mammal, more preferably a human.
  • the invention relates to a peptide as defined above, for use in the prevention and/or the treatment of a viral infection, preferably a coronavims infection, more preferably an infection by a coronavims selected from the list consisting of SARS-CoV, MERS-CoV and SARS-CoV2.
  • the present invention also relates to a method of prevention and/or treatment of a viral infection, preferably a coronavims infection, more preferably an infection by a coronavims selected from the list consisting of SARS-CoV, MERS-CoV and SARS-CoV2, in a subject in need thereof comprising administering to said subject an effective amount of a peptide as defined above.
  • the present invention also relates to the use of a peptide as defined above in the manufacture of a medicament for the prevention and/or the treatment of a viral infection, preferably a coronavims infection, more preferably an infection by a coronavirus selected from the list consisting of SARS-CoV, MERS-CoV and SARS-CoV2.
  • the peptides of the invention are indeed able to bind the viral protein Spike, in particular the Spike protein of coronavimses, more particularly the Spike protein of SARS-CoV, MERS-CoV and/or SARS-CoV2. This interaction can be readily verified by techniques known to those skilled in the art such as those described in the examples of the present application.
  • the peptide of the invention is preferably used to coat the oral cavity, the nasal cavity and/or the eye surface.
  • the peptide of the invention is preferably administered to a subject in the form of a solution, a syrup, a tablet (such as a sublingual tablet), an eye-wash, a powder, a spray (such as an oral or nasal spray), a capsule, a gum, a pastille or an emulsion.
  • the present invention relates to a peptide as defined above for use in the prevention of SARS-CoV2 infection, wherein said peptide is administered in the form of a solution, a syrup, a tablet (such as a sublingual tablet), an eye-wash, a powder, a spray (such as an oral or nasal spray), a capsule, a gum, a pastille a lipstick or an emulsion.
  • the invention relates to a diagnostic or imaging reagent comprising a peptide as defined above.
  • a reagent according to the invention is particularly adapted for immunoassays, such as ELISA tests, and can be used for the detection of viral particles in biological samples, such as saliva or epithelial cells.
  • the invention also relates to the use of a peptide as defined above as a diagnostic or imaging reagent to detect viruses, in particular coronavimses, more particularly SARS-CoV, MERS-CoV or SARS-CoV2.
  • the peptide is linked covalently to a fluorescent or radioactive agent.
  • Covalent coupling of a labeling agent, for example a fluorescent or radioactive agent, to the peptide may be achieved by incorporating the labeling agent at the N-or C-terminal end of the peptide during chemical synthesis of the peptide, or incorporating a reactive group in a recombinant or synthetic peptide, and then using the group to link the labeling agent covalently.
  • a subject of the present invention is also the use of a peptide as defined above, in vitro or ex vivo , for diagnosing an infection by viruses, in particular by coronaviruses, more particularly by SARS-CoV, MERS-CoV or SARS-CoV2.
  • Another subject of the present invention is a peptide as defined above for use, in vivo, for diagnosing an infection by viruses, in particular by coronaviruses, more particularly by SARS- CoV, MERS-CoV or SARS-CoV2.
  • a subject of the present invention is also the use of a peptide as defined above, as a research tool, in particular for studying the Spike protein-hACE2 interaction.
  • the invention in another aspect, relates to a polynucleotide encoding a peptide as defined above.
  • the isolated, synthetic or recombinant polynucleotide may be DNA, cDNA, RNA or combination thereof, either single- and/or double-stranded.
  • the polynucleotide comprises a coding sequence which is optimized for the host in which the peptide is expressed.
  • the invention relates to an expression vector comprising a polynucleotide encoding a peptide as defined above.
  • said vector is an expression vector capable of expressing said polynucleotide when transfected or transformed into a host cell, such as a mammalian, bacterial or fungal cell.
  • the polynucleotide is inserted into the expression vector in proper orientation and correct reading frame for expression.
  • the polynucleotide is operably linked to at least one transcriptional regulatory sequence and, optionally to at least one translational regulatory sequence.
  • Recombinant vectors include usual vectors used in genetic engineering and gene therapy including for example plasmids and viral vectors.
  • the invention relates to a host cell modified with a polynucleotide as defined above or an expression vector as defined above.
  • the polynucleotide, vector, cell of the invention are useful for the production of the peptide of the invention using well-known recombinant DNA techniques.
  • the invention relates to a pharmaceutical composition, comprising at least: (i) a peptide as defined above, a polynucleotide encoding said peptide, and/or an expression vector comprising said polynucleotide, and (ii) a pharmaceutically acceptable carrier.
  • a further aspect of the invention relates to a polynucleotide, a vector and/or a modified host cell of the invention for use as a medicament.
  • the invention also provides also a kit comprising : (a) a container that contains one or more of: a peptide, polynucleotide, recombinant vector, modified host cell, pharmaceutical composition, diagnostic or imaging reagent of the invention, in solution or in lyophilized form; (b) optionally, a second container containing a diluent or reconstituting solution for the lyophilized formulation; and (c) optionally instructions for the use of the solution(s) and/or the reconstitution and/or use of the lyophilized formulation(s).
  • the polynucleotide according to the invention is prepared by the conventional methods known in the art. For example, it is produced by amplification of a nucleic sequence by PCR or RT- PCR, by screening genomic DNA libraries by hybridization with a homologous probe, or else by total or partial chemical synthesis.
  • the recombinant vectors are constructed and introduced into host cells by the conventional recombinant DNA and genetic engineering techniques, which are known in the art.
  • Figure 1 Molecular modeling of hACE2 and cell-surface Spike protein of SARS-CoV-2 from 6m0j. The molecular modeling has been focused on the interacting fragments of hACE2 protein and SARS-CoV-2 S protein.
  • Figure 2. Highlighting the surface interaction of the a-helix of hACE2 and cell- surface Spike protein of SARS-CoV-2.
  • FIG. 3 Highlights on the hACE2 a-helix interacting with the cell- surface Spike protein of SARS-CoV-2. The essential interacting residues of the helix are shown in grey and the residues not directly involved in the interaction are shown in black.
  • Figure 4. Highlights on side chains interactions.
  • A. The a-helices of hACE2 highlighting the Ys3.
  • B. A25/I1Y25 mutation superimposed with the hACE2 full protein with Y83.
  • FIG. 6 Peptide-mimics of hACE2 show high anti-infective efficacy and are devoid of cell toxicity a.
  • Percent inhibition of SARS-Cov-2 replication Vero-E6 cells were infected with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.1 in the presence of 10 peptides (H20, H21, H22, H27, H30, H40, H2I/I2I/N33/M33, HI, H38 and H39 as controls) at 10 mM for 2 h. Then, the virus was removed, and cultures were washed, incubated for 48 h, before supernatant was collected to measure virus replication by ELISA.
  • MOI multiplicity of infection
  • SARS-CoV-2 titer reduction in Vero-E6 Cells were infected with SARS-CoV- 2 in triplicate at a multiplicity of infection (MOI) of 0.1 in the presence of different concentrations (from 0.01 to 10 pM) of peptides H2I/I2I/N33/M33, H41 and H34 for 2 h. Then the virus was removed, and cultures were washed and incubated for 72 h to measure virus production by plaque assay c. Cell cytotoxicity in Vero-E6 cells.
  • MOI multiplicity of infection
  • Cells were infected with SARS-CoV-2 in triplicate at a multiplicity of infection (MOI) of 0.3 in the presence of different concentrations (from 0.01 to 10 mM) of peptides H2I/I2I/N33/M33, H41 or H34 for 2 hr, after which the vims was removed, and cultures were washed in, incubated for 72 h to measure vims production by plaque assay e. Dose-inhibition curve in Calu-3.
  • MOI multiplicity of infection
  • Cells were infected with SARS-CoV-2 at respectively a multiplicity of infection (MOI) of 0.3 in the presence of 6 different concentrations (from 0.01 to 10 mM) of peptides HI, H38, H40, H2I/I2I/N33/M33, H41, H34, for 2 h. Then, the vims was removed, and cultures were washed in, incubated for 48 h, before supernatant was collected to measure vims replication by ELISA. Data are combined from 3 to 6 independent experiments and expressed as percent of inhibition compared to untreated SARS CoV-2-infected Vero-E6 cells.
  • MOI multiplicity of infection
  • Data fitted in the sigmoidal dose-response curve represent the means (+SD) of at least three independent experiments and are expressed as percent of inhibition compared to untreated SARS CoV-2-infected Vero-E6 cells f.
  • Cell cytotoxicity in Calu-3 cells Cell viability was measured by MTT assays after treatment with vehicle 0, 0.1, 1 or 10 mM of H2I/I2I/N33/M33, H41 or H34 for 24, 48, or 72 h. Cell death was measured by flow cytometry using annexin-V- APC and PI staining in cells treated with vehicle or 10 mM H2I/I2I/N33/M33, H41 or H34 for 24, 48, or 72 h.
  • FIG. 7 Inhibition of SARS-CoV-2 replication in Vero-E6 cells using H41 and H34.
  • Vero-E6 cells were infected with SARS-CoV-2 at a multiplicity of infection (MOI) of 0.1 in the presence of H41 and H34 (H2I/I2I/N33/M33 and H38 were used as controls) at 10 mM for 2 h. Then, the vims was removed, and cultures were washed, incubated for 48 h, before supernatant was collected to measure vims replication by ELISA. Histograms represent the means of three independent experiments (each performed by duplicate; dots above). Data is expressed as compared to untreated SARS CoV-2-infected Vero-E6 cells
  • FIG. 8 Helical peptide-mimics of hACE2 strongly bind to the spike RBD.
  • the Fc-tagged 2019-nCoV RBD-SD1 (Sanyou Biopharmaceuticals Co. Ltd) was immobilized to an anti human capture (AHC) sensortip (ForteBio) using an Octet RED96e system (ForteBio). The sensortip was then dipped into a) 0.1 mM solution of hACE2 (Sanyou Biopharmaceuticals Co.
  • Peptides syntheses Peptides were produced by GENECUST or manually synthesized from Fmoc-protected amino acids utilizing standard solid phase peptide synthesis (SPPS) methods. Solid-phase peptide syntheses were performed in polypropylene Torviq syringes (10 or 20 mL) fitted with a polyethylene porous disk at the bottom and closed with an appropriate piston. Solvent and soluble reagents were removed through back and forth movements. The appropriate protected amino acids were sequentially coupled using PyOxim/Oxyma as coupling reagents.
  • SPPS solid phase peptide synthesis
  • the peptides were cleaved from the chlorotrityl or rink amide resin with classical cleavage cocktail TFA/TIS/H20 (95:2.5:2.5).
  • the crude products were purified using preparative scale HPLC.
  • the final products were characterized by analytical LCMS and NMR. All tested compounds were TFA salts and were at least 95% pure. Detailed NMR studies were performed for the relevant peptides and assignment tables are provided in the Supporting Information.
  • Method A Analytical HPLC was conducted on a X-Select CSH C18 XP column (30 mm x 4.6 mm i.d., 2.5 pm), eluting with 0.1% formic acid in water (solvent A) and 0.1% formic acid in acetonitrile (solvent B), using the following elution gradient: 0-3.2 min, 0-50% B; 3.2-4 min, 100% B. Flow rate was 1.8 mL/min at 40 °C.
  • MS mass spectra
  • ES+ electrospray positive ionization
  • ES- electrospray negative ionization
  • the cone voltage was 20 V.
  • Method B Analytical HPLC was conducted on a X-Select CSH C18 XP column (30 mm x 4.6 mm i.d., 2.5 pm), eluting with 0.1% formic acid in water (solvent A) and 0.1% formic acid in acetonitrile (solvent B), using the following elution gradient: 0-3.2 min, 5-100% B; 3.2-4 min, 100% B.
  • Preparative scale purification of peptides was performed by reverse phase HPLC on a Waters system consisting of a quaternary gradient module (Water 2535) and a dual wavelength UV/visible absorbance detector (Waters 2489), piloted by Empower Pro 3 software using the following columns: preparative Macherey- Nagel column (Nucleodur HTec, C18, 250 mm x 16 mm i.d., 5 pm, 110 A) and preparative Higgins analytical column (Proto 200, C18, 150 mm x 20 mm i.d., 5 pm, 200 A) at a flow rate of 14 mL/min and 20 mL/min, respectively.
  • preparative Macherey- Nagel column Nucleodur HTec, C18, 250 mm x 16 mm i.d., 5 pm, 110 A
  • preparative Higgins analytical column Proto 200, C18, 150 mm x 20 mm i.d., 5 pm, 200 A
  • a 0.6 mL microcentrifuge tube was charged with 180 pL of phosphate buffer pH 7.4, 10 pL of enzyme (0.05 mg/mL stock solution in phosphate buffer pH 7.4), 10 pL of peptide (10 mM stock solution in DMSO). The resulting reaction mixture was capped and incubated at room temperature for 3 hours. 20 pL of the crude reaction was quenched by addition of 180 pL of 50% water: 50% acetonitrile and was subjected to LCMS analysis.
  • CD experiments were acquired on a Jasco J-815 CD spectropolarimeter with a Peltier temperature-controlled cell holder (30°C) over the wavelength range 190-270 nm.
  • Peptide samples were prepared at a concentration of 50 pM in 10 mM sodium phosphate buffer, pH 7.4, using a quartz cell of 1 mm path length. Measurements were taken every 0.2 nm at a scan rate of 10 nm/min.
  • Lyophilized peptide was dissolved at 1 mM concentration in 550 pL of H20/D20 (90:10 v/v).
  • Sodium 4,4-dimethyl-4-silapentane-l-sulfonate-d6 (DSS, from Sigma Aldrich) was added at a final concentration of 0.11 mM for chemical shift calibration.
  • NMR experiments were recorded on a Bruker Avance III 500 MHz spectrometer equipped with a TCI 1H/13C/15N cryoprobe with Z-axis gradient.
  • NMR spectra were processed with TopSpin 3.2 software (Bruker) and analysed with NMRF AM-SPARKY program.43 1H, 13C, and 15N resonances were assigned using ID 1H WATERGATE, 2D 1H-1H TOCSY (DIPSI-2 isotropic scheme of 80 ms duration), 2D 1H-1H ROESY (300 ms mixing time), 2D 1H-13C HSQC, 2D 1H-15N HSQC, and 2D 1H-13C HMBC recorded at 25°C. 1H chemical shift was referenced against DSS 1H signal and 13C, 15N chemical shifts were referenced indirectly.
  • Fc-tagged 2019-nCoV RBD-SD1 was immobilized to an anti-human capture (AHC) sensortip (ForteBio) using an Octet RED96e (ForteBio). The sensortip was then dipped into 100 nM hACE2 (Sanyou Biopharmaceuticals Co.
  • hACE2 peptide mimics Cells and virus preparation.
  • Calu-3 (ATCC HTB55) and Vero-E6 (ATCC CRL-1586) cells were purchased from the American Type Culture Collection and routinely checked for mycoplasma contamination. Cells were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with non-essential amino acids, penicillin-streptomycin, and 10% v/v fetal bovine serum.
  • DMEM Dulbecco's Modified Eagle Medium
  • the SARS-CoV-2 clinical isolate was obtained from BAL of a symptomatic infected patient (#SARS-CoV-2/PSL2020, available at Pitie-Salpetriere hospital, Paris (France)).
  • the patient recruited for virus isolation and culture was in intensive care unit in the Pitie Salpetriere hospital.
  • the patient underwent a bronchoalveolar lavage for clinical purpose (seeking for a bacterial pulmonary infection).
  • the protocol was approved by our institution’s ethics committee (Immuno-COVID-REA, CER-Sorbonne Universite, no. CER-SU-2020-31).
  • BAL 0.5 mL was mixed with an equal volume of DMEM without FBS, supplemented with 25 mM Hepes, double concentration of penicillin- streptomycin and miconazole (Sigma), and added to 80% confluent Vero-E6 cells monolayer seeded into a 25 cm2 tissue culture flask.
  • Infectious viral particles were measured by a standard plaque assay previously described with fixation of cells 72 h post infection. Accordingly, the viral titer of SARS-CoV-2/PSL2020 P#2 stock was about 5.3 10 5 PFU mL 1 .
  • Vero-E6 or Calu-3 (1 x 10 5 cells mL-1) were seeded into 24 wells plates in infectious media and treated with different concentrations of the peptides (from 0.1 to 10 mM). After 30 min at room temperature, cells were infected with 0.1 multiplicity of infection (MOI) (Vero-E6) or 0.3 MOI (Calu-3) of SRAS-CoV-2 (SARS-CoV-2/PSL2020 P#2 stock) in infectious media.
  • MOI multiplicity of infection
  • SRAS-CoV-2 SARS-CoV-2/PSL2020 P#2 stock
  • This a-helix interacting with the protein S of SARS-CoV-2 is composed of 27 residues (I1ACE19-45) as shown in SEQ ID NO: 15: S19T20I21E22E23O24A25K26T27F28L29D30K31F32N33H34E35A36E37D38L39F40Y41Q42S43S44L45
  • T 27 interacts with a shallow hydrophobic pocket defined by A 475 , Y 473 and Y 489 ; in the meantime, the carbon chain of K 31 nicely extends in a tiny groove defined by Y 489 and F 456 to finally hydrogen bonds with Q 493 .
  • F 28 and H 34 are both in weak interaction with the surface above F 486 /Y 489 and L 455 respectively.
  • H34 also makes an H-bond with Y 453 , and Y 41 with T 500 and N 501 .
  • Ys 3 of hACE2 and F 486 of the protein S are in close proximity together with F 28 . This interaction might stabilize the overall structure of the complex.
  • a 25 which is not involved in any interaction, might be mutated to Y 25 or preferably to homoY 25 .
  • MM calculation highlighted a better overlapping of aromatic ring with homoY instead of Y.
  • EXAMPLE II Design and characterization of q-helix peptide mimics In the sequence of the a-helix, 13 residues (S19, Q24, T27, F28, D30, K31, H34, E35, E37, D38, Y41, Q 42 , L 45 ) appeared to be crucial for the interaction with protein S of SARS-Cov-2 and 14 residues (T20, I21, E22, E23, A25, K26, L29, F32, N33, A36, L39, F40, S43, S44) appeared to be non- essential for the interaction but may be important for helical sequence folding in the protein context.
  • the synthesis of the peptides of the invention was primarily directed by the will to provide a simple drug easy to produce quickly on a large scale, without technical constraints requiring sometimes laborious development.
  • the use of mostly natural amino acids was preferred since it can facilitate the essential stages of the development of therapeutic tools, particularly for pharmacokinetics, pre-clinical and clinical toxicity aspects.
  • the design of the a-helix peptide mimics might be optimized regarding the binding affinity in term of entropy loss.
  • the helical structure to mimic involves a favorable sequence in the N-terminus side around a “capping box”, i.e. SX1X2E (SEQ ID NO: 147).
  • This feature might be of crucial importance, especially for a peptide extracted from the hACE2 full protein context.
  • This capping box involves a reciprocal backbone-side-chain hydrogen-bonding interaction between the oxygen atom of Serine side chain hydroxyl function and the Glutamate NH involved in the backbone, favoring thus the helix initiation.
  • the Xi and X2 residues of the capping box of hACE2 correspond respectively to T and I. Since both residues are not involved in crucial interaction, increasing hydrophobicity in this position might enhance the helical propensity. The mutations of both T and I by residues favoring helical content will thus be considered.
  • ⁇ a scramble peptide from peptide HI was designed as a negative control for the binding and infectivity studies using a srambler tool.
  • ⁇ a control peptide without the capping box was used. Noticeably, best helical contents were observed for peptide mimics with free N-terminus. Regarding the C-terminus, very similar results were observed for the C-carboxamide protected peptide mimics and the free carboxylate peptide. The C-terminus protected peptide was chosen for further development.
  • the A25 to L25 substitution led to a high increase of helical content, from 8,33 to 21,02% for the peptide with C-terminus protected (21,58% for N- and C- termini protected).
  • the A36 to L36 substitution led again to a slight increase of helical content, from 21,02 to 32,54% for the C-terminus protected peptide.
  • the importance of the four residues in N-terminus was then evaluated considering the consensus sequence “SXXE” (SEQ ID NO: 147) reported as a capping box and considering that T20 hydroxyl function is not involved in any interaction and that increasing hydrophobicity in this position might enhance the helical propensity.
  • T20 was first replaced by a Leucine (Peptide H5).
  • the T20/L20 led again to an increase of the helical content with the same trends as previously described for N- and C- termini modifications, from 32,54% to 38,39%.
  • a Leucine-scanning of the XX residues (i.e. TI) of this capping Box was then performed. If the same trends as previously described for N- and C- termini modifications were observed, the I21/L21 (Peptide H6) slightly improves the helical content as compared to peptide H4.
  • the A43/L43 mutation from peptide H15 to peptide H17 led again to an improvement of the helical content, from 50,51% to 54,22%. Similar trends were observed for the A40/L40 mutation of peptide H18, from 50,51% to 55,19%. A new peptide was designed combining both mutations, A40/L40 and A43/L43 leading to peptide H20. A gap was reached here with 63,71% of helical content. Of note, the A20/L20 mutation from peptide H15 to peptide H19 led a slight decrease of the helical content, from 50,51% to 47,42%. Leucine is thus not recommended in this position.
  • L39 is not crucial in term of peptide/protein S interaction
  • its mutation form L39 to P39 seemed to be more suitable than the previous one. Indeed, again, apart from structural impact, this mutation will lead to the loss of Leucine side chain not involved in the direct interaction with the protein S of SARCoV-2. Nevertheless, useful cis and trans-3-substituted prolinoleucine analogues proven to be highly efficient constrained leucine surrogates and they might be used for affinity improvement if required.
  • the peptide H27 was thus drawn from peptide H21 and its helical content calculated.
  • the second phase of the peptide mimics maturation was related to the identification of immunogenicity. Indeed, since peptides triggering immune response might be neutralized and thus lose their therapeutic potential, the immunogenicity was predicted and optimized using the semi-empirical method reported by Kolaskar and Tongaonkar based on the physicochemical properties of amino acid residues and their frequencies of occurrence in experimentally known segmental epitopes (Kolaskar & Tongaonkar, FEBS Fett. 1990, 276(1 -2): 172- 174).
  • Position 33 is the keystone of calculated immunogenicity.
  • the position 33 involves a residue (N33) not crucial for the interaction of the helix with the protein S but crucial for the helicity and for immunogenicity.
  • the only possible mutation on this position is N33 to M33 to increase the helical content together with avoiding calculated immunogenicity.
  • D 38 /P 38 and L 39 /P 39 mutations proven by molecular modeling analyses to mimic the kink, D 38 is a crucial residue for the interaction with protein S of SARCoV-2 and thus the L 39 /P 39 appeared suitable for further development. Indeed, if peptide H27 appeared with a calculated immunogenicity, the mutation of L 33 to N 33 and M 33 led to peptides 127 and H27/I27/ N33/M33 devoid of calculated immunogenicity.
  • H2I/I2I/N33/M33, H41 and H34 were evaluated for their ability to bind to SARS-CoV-2 spike RBD (Figure 8) using biolayer Interferometry (BLI) with an Octet RED96e system (ForteBio). hACE2 was used as a positive control ( Figure 8a).

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Abstract

L'invention concerne un nouveau groupe de peptides qui imitent une structure d'hélice α de l'enzyme 2 de conversion de l'angiotensine humaine (hACE2) pour lier la protéine de spicule (protéine S) de virus, en particulier de coronavirus. Ces peptides peuvent être utilisés dans la thérapie, la prophylaxie, le diagnostic, l'imagerie médicale, le criblage de médicaments et la recherche.
EP21722499.7A 2020-05-06 2021-05-05 Peptides pour la prévention ou le traitement d'infections virales Pending EP4146242A1 (fr)

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