WO2022079205A1 - Utilisation de polypeptides d'ifn-alpha pour le traitement d'infections à coronavirus - Google Patents

Utilisation de polypeptides d'ifn-alpha pour le traitement d'infections à coronavirus Download PDF

Info

Publication number
WO2022079205A1
WO2022079205A1 PCT/EP2021/078527 EP2021078527W WO2022079205A1 WO 2022079205 A1 WO2022079205 A1 WO 2022079205A1 EP 2021078527 W EP2021078527 W EP 2021078527W WO 2022079205 A1 WO2022079205 A1 WO 2022079205A1
Authority
WO
WIPO (PCT)
Prior art keywords
ifn
alpha
polypeptide
seq
amino acid
Prior art date
Application number
PCT/EP2021/078527
Other languages
English (en)
Inventor
Fabrizio Mammano
Jérôme ESTAQUIER
Manuel Rosa Calatrava
Thomas Julien
Original Assignee
INSERM (Institut National de la Santé et de la Recherche Médicale)
Ecole Normale Supérieure de Lyon
Universite De Paris
Université Claude Bernard Lyon 1
UNIVERSITé LAVAL
Centre National De La Recherche Scientifique (Cnrs)
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 INSERM (Institut National de la Santé et de la Recherche Médicale), Ecole Normale Supérieure de Lyon, Universite De Paris, Université Claude Bernard Lyon 1, UNIVERSITé LAVAL, Centre National De La Recherche Scientifique (Cnrs) filed Critical INSERM (Institut National de la Santé et de la Recherche Médicale)
Publication of WO2022079205A1 publication Critical patent/WO2022079205A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • A61K38/212—IFN-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • 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
    • 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

Definitions

  • the present invention is in the field of medicine and in particular virology.
  • Coronaviridae is a family of enveloped, positive-sense, single- stranded RNA viruses.
  • the viral genome is 26-32 kilobases in length.
  • the particles are typically decorated with large ( ⁇ 20 nm), club- or petal-shaped surface projections (the “peplomers” or “spikes”), which in electron micrographs of spherical particles create an image reminiscent of the solar corona.
  • peplomers club- or petal-shaped surface projections
  • the World Health Organization has named the severe pneumonia caused by this new coronavirus COVID- 19 (for Corona Virus Disease 2019, WHO, 2020) Since its emergence, the SARS- CoV-2 has spread across the five continents causing more than one million of deaths in the world.
  • COVID-19 pandemic in addition to the containment measures implemented in many countries, several projects have been launched around the world to understand the viral evolution and the pathophysiological consequences of the infection in order to identify therapeutic targets and to implement innovative therapies.
  • type I IFN deficiency in the blood is now considered as a hallmark of severe CO VID- 19 and provides a rationale to consider that severe COVID-19 patients might be potentially relieved from the IFN deficiency by IFN administration (Hadjadj J. et al. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients. Science. 2020 Aug 7;369(6504):718-724).
  • Type 1 interferons (IFN-I) are indeed crucial cytokines of the innate immunity.
  • IFN-I interferon stimulated genes
  • IFN-alpha2 has also a broad spectrum of antiviral activities, and was also used recently to treat SarsCoV-2 infection in the clinics (PeredaR. et al., Journal of Interferon and cytokine research. 2020; Wang B. et al., BMC infectious diseases. 2020).
  • the role played by the different IFN-alpha subtypes to modulate viral infection and pathogenesis mediated by SARS-CoV-2 has never been investigated.
  • the present invention is defined by the claims.
  • the present invention relates to the use of an IFN-alpha polypeptide for the treatment of SARS-CoV-2 infection.
  • IFN-alpha subtypes represent better alternatives to IFN-beta to modulate viral infection and pathogenesis mediated by SARS-CoV-2.
  • the first object of the present invention relates to a method of treating a coronavirus infection in a subject in need thereof comprising administrating to the subject a therapeutically effective amount of an IFN-alpha polypeptide provided that said polypeptide is not an IFN-alpha2 polypeptide.
  • coronavirus has its general meaning in the art and refers to any member of members of the Coronaviridae family.
  • Coronavirus is a virus whose genome is plus- stranded RNA of about 27 kb to about 33 kb in length depending on the particular virus.
  • the virion RNA has a cap at the 5’ end and a poly A tail at the 3 ’ end.
  • the length of the RNA makes coronaviruses the largest of the RNA virus genomes.
  • coronavirus RNAs encode: (1) an RNA-dependent RNA polymerase; (2) N-protein; (3) three envelope glycoproteins; plus (4) three non- structural proteins. These coronaviruses infect a variety of mammals and birds.
  • Coronaviruses are transmitted by aerosols of respiratory secretions. Coronaviruses are exemplified by, but not limited to, human enteric coV (ATCC accession # VR-1475), human coV 229E (ATCC accession # VR-740), human coV OC43 (ATCC accession # VR-920), Middle East respiratory syndrome-related coronavirus (MERS- Cov) and SARS-coronavirus (Center for Disease Control), in particular SARS-CoVl and SARS-CoV2.
  • human enteric coV ATCC accession # VR-1475
  • human coV 229E ATCC accession # VR-740
  • human coV OC43 ATCC accession # VR-920
  • Middle East respiratory syndrome-related coronavirus MERS- Cov
  • SARS-coronavirus Center for Disease Control
  • the IFN-alpha polypeptide of the present invention is particularly suitable for inhibiting the replication of SARS-CoV-2 as demonstrated in EXAMPLE.
  • the IFN-alpha polypeptide of the present invention is suitable for the treatment of Severe Acute Respiratory Syndrome (SARS). More particularly, the IFN-alpha polypeptide of the present invention is suitable for the treatment of COVID-19.
  • SARS Severe Acute Respiratory Syndrome
  • the subject can be human or any other animal (e.g., birds and mammals) susceptible to coronavirus infection (e g. domestic animals such as cats and dogs; livestock and farm animals such as horses, cows, pigs, chickens, etc.).
  • said subject is a mammal including a non-primate (e.g., a camel, donkey, zebra, cow, pig, horse, goat, sheep, cat, dog, rat, and mouse) and a primate (e.g., a monkey, chimpanzee, and a human).
  • the subject is a non-human animal.
  • the subject is a farm animal or pet.
  • the subject is a human.
  • the subject is a human infant. In some embodiments, the subject is a human child. In some embodiments, the subject is a human adult. In some embodiments, the subject is an elderly human In some embodiments, the subject is a premature human infant.
  • treatment refers to both prophylactic or preventive treatment as well as curative or disease modifying treatment, including treatment of patient at risk of contracting the disease or suspected to have contracted the disease as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition, and includes suppression of clinical relapse.
  • the treatment may be administered to a patient having a medical disorder or who ultimately may acquire the disorder, in order to prevent, cure, delay the onset of, reduce the severity of, or ameliorate one or more symptoms of a disorder or recurring disorder, or in order to prolong the survival of a patient beyond that expected in the absence of such treatment.
  • therapeutic regimen is meant the pattern of treatment of an illness, e.g., the pattern of dosing used during therapy.
  • a therapeutic regimen may include an induction regimen and a maintenance regimen.
  • the phrase “induction regimen” or “induction period” refers to a therapeutic regimen (or the portion of a therapeutic regimen) that is used for the initial treatment of a disease.
  • the general goal of an induction regimen is to provide a high level of drug to a patient during the initial period of a treatment regimen.
  • An induction regimen may employ (in part or in whole) a "loading regimen", which may include administering a greater dose of the drug than a physician would employ during a maintenance regimen, administering a drug more frequently than a physician would administer the drug during a maintenance regimen, or both.
  • maintenance regimen refers to a therapeutic regimen (or the portion of a therapeutic regimen) that is used for the maintenance of a patient during treatment of an illness, e.g., to keep the patient in remission for long periods of time (months or years).
  • a maintenance regimen may employ continuous therapy (e.g., administering a drug at a regular interval, e.g., weekly, monthly, yearly, etc.) or intermittent therapy (e.g., interrupted treatment, intermittent treatment, treatment at relapse, or treatment upon achievement of a particular predetermined criteria [e.g., pain, disease manifestation, etc.]).
  • polypeptide As used herein, the terms “polypeptide”, “peptide”, and “protein” are used interchangeably herein to refer to polymers of amino acids of any length. The terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, phosphorylation, or conjugation with a labeling component. Polypeptides when discussed in the context of therapy refer to the respective intact polypeptide, or any fragment or genetically engineered derivative thereof, which retains the desired biochemical function of the intact protein.
  • IFN-alpha polypeptide refers to a subgroup of type I interferon proteins that bind to a specific cell surface receptor complex known as the IFN-a receptor (IFNAR) that consists of IFNAR1 and IFNAR2 chains.
  • IFN-a proteins are produced mainly by plasmacytoid dendritic cells (pDCs). They are mainly involved in innate immunity against viral infection.
  • the genes responsible for their synthesis come in 13 subtypes that are called IFNA1, IFNA2, IFNA4, IFNA5, IFNA6, IFNA7, IFNA8, IFNA10, IFNA13, IFNA14, IFNA16, IFNA17, IFNA21.
  • IFN-alpha polypeptide encompasses derivatives of IFN-alpha polypeptides that are are derived (e g., are chemically modified relative to the naturally occurring peptide) to alter certain properties such as serum half-life.
  • IFN-alpha polypeptide includes IFN- alpha polypeptides that are conjugated to polyethylene glycol (“PEGylated IFN-a”), and the like. For instance PEGylated IFN-a, and methods for making same, is discussed in, e.g., U.S. Pat. Nos. 5,382,657; 5,951,974; and 5,981,709.
  • the IFN-alpha polypeptide of the present invention is an IFN-alpha 1 polypeptide, an IFN-alpha 4 polypeptide, an IFN-alpha 5 polypeptide, an IFN-alpha 6 polypeptide, an IFN-alpha 7 polypeptide, an IFN-alpha 8 polypeptide, an IFN-alpha 10 polypeptide, an IFN-alpha 14 polypeptide, an IFN-alpha 16 polypeptide, an IFN-alpha 17 polypeptide, or an IFN-alpha 21 polypeptide. More particularly, the IFN-alpha polypeptide of the present invention is an IFN-alpha 8 polypeptide, an IFN-alpha 10 polypeptide, or an IFN-alpha 14 polypeptide.
  • the IFN-alpha polypeptide of the present invention does not consist of the amino acid sequence of SEQ ID NO:2.
  • the IFN-alpha 1 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO:1.
  • the IFN-alpha 4 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 3.
  • the IFN-alpha 5 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 4.
  • the IFN-alpha 6 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 5.
  • the IFN-alpha 7 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 6.
  • the IFN-alpha 8 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO:7.
  • the IFN-alpha 10 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 8.
  • the IFN-alpha 14 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 9.
  • the IFN-alpha 16 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 10. In some embodiments, the IFN-alpha 17 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 11.
  • the IFN-alpha 21 polypeptide has an amino acid sequence having at least 90% of identity with SEQ ID NO: 12.
  • the comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm, as described below.
  • the percent identity between two amino acid sequences can be determined using the Needleman and Wunsch algorithm (NEEDLEMAN, and Wunsch).
  • the percent identity between two nucleotide or amino acid sequences may also be determined using for example algorithms such as EMBOSS Needle (pair wise alignment; available at www.ebi.ac.uk).
  • EMBOSS Needle may be used with a BLOSUM62 matrix, a “gap open penalty” of 10, a “gap extend penalty” of 0.5, a false “end gap penalty”, an “end gap open penalty” of 10 and an “end gap extend penalty” of 0.5.
  • the “percent identity” is a function of the number of matching positions divided by the number of positions compared and multiplied by 100. For instance, if 6 out of 10 sequence positions are identical between the two compared sequences after alignment, then the identity is 60%. The % identity is typically determined over the whole length of the query sequence on which the analysis is performed. Two molecules having the same primary amino acid sequence or nucleic acid sequence are identical irrespective of any chemical and/or biological modification.
  • a first amino acid sequence having at least 90% of identity with a second amino acid sequence means that the first sequence has 90; 91; 92; 93; 94; 95; 96; 97; 98; 99 or 100% of identity with the second amino acid sequence.
  • the IFN-alpha polypeptide of the present invention is administered to the subject in combination with at least one other therapeutic agent, preferably in combination with at least one other antiviral agent, more preferably in combination with at least one other antiviral agent selected from the group consisting of remdesivir, lopinavir, ritonavir, hydroxycholoroquine, and chloroquine.
  • the term "therapeutically effective amount” refers to a sufficient amount of the IFN-alpha polypeptide to treat a coronavirus infection at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the compounds and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment.
  • the specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound employed; the specific composition employed, the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination with the specific agonist employed; and like factors well known in the medical arts.
  • the daily dosage of the products may be varied over a wide range from 0.01 to 1,000 mg per adult per day.
  • the compositions contain 0.01, 0.05, 0.1, 0.5, 1.0, 2.5, 5.0, 10.0, 15.0, 25.0, 50.0, 100, 250 and 500 mg of the active ingredient for the symptomatic adjustment of the dosage to the patient to be treated.
  • a medicament typically contains from about 0.01 mg to about 500 mg of the active ingredient, preferably from 1 mg to about 100 mg of the active ingredient.
  • An effective amount of the drug is ordinarily supplied at a dosage level from 0.0002 mg/kg to about 20 mg/kg of body weight per day, especially from about 0.001 mg/kg to 7 mg/kg of body weight per day.
  • the IFN-alpha polypeptide of the present invention is administered in the form of a pharmaceutical composition.
  • composition refers to a composition described herein, or pharmaceutically acceptable salts thereof, with other agents such as carriers and/or excipients.
  • the pharmaceutical compositions as provided herewith typically include a pharmaceutically acceptable carrier.
  • the term “pharmaceutically acceptable carrier” includes any and all solvents, diluents, or other liquid vehicle, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants and the like, as suited to the particular dosage form desired.
  • Remington's Pharmaceutical-Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980) discloses various carriers used in formulating pharmaceutical compositions and known techniques for the preparation thereof.
  • FIGURES are a diagrammatic representation of FIGURES.
  • the upper panel represents the number of copies of SARS CoV-2 genomes measured in the first series of RT-qPCR amplifications, performed on the RNA extracted from the supernatant of untreated cultures or cultures treated with IFN-alpha 1, 2, 4,5 ,6, 7, IFN-beta, or Remdesivir.
  • the lower panel shows the number of copies of SARS CoV-2 genomes measured in the second series of RT-qPCR amplifications, performed on the RNA extracted from the supernatant of untreated cultures or cultures treated with IFN-alpha 8, 10, 14, 16, 17, 21 IFN-beta, or Remdesivir.
  • the extent of SARS CoV-2 replication on the susceptible Vero-E6 cells was measured in untreated cultures (left white column, in the upper and lower panels) and cultures that were treated with two concentrations (2 ng/ml, and 0.4 ng/ml) of each IFN-alpha subtype or IFN- beta, as indicated.
  • Remdesivir 5 uM was also used.
  • Cell cultures were pretreated for 24h with the indicated concentrations of the molecules, followed by exposure of the cells to a SARS CoV-2 virus inoculum (MOI 0.01) for Ih. After this incubation, cells were washed to eliminate excess virus and cultured in the presence of the indicated concentrations of the molecules. 54 hours after exposure to the virus, virus containing supernatants were collected, viral RNA was extracted and the amount of virus present was quantified by a RT-qPCR amplification targeting the nspl4 viral gene.
  • the main aim of the inventors is to explore the respective efficacy of IFN-alpha polypeptides in controlling SARS-CoV-2 replication and pathogenesis of coronavirus disease 19 (COVID- 19).
  • Type 1 interferons are indeed crucial cytokines of the innate immunity.
  • IFN-I the human genome encodes a single IFN-beta and 12 subtypes of IFN-alpha (75-99% of identity at the amino acid level), all of which bind to the same heterodimeric receptor (IFNAR) expressed on the cell surface 28 ' 31 , leading to the expression of hundreds of interferon stimulated genes (ISGs) 32 .
  • ISGs interferon stimulated genes
  • Some of the ISGs have direct antiviral function, while others link innate and adaptive immunity.
  • the similarities and differences of the IFN-alpha subtypes were recently reviewed 33 . They emerged by gene duplication events 34, 35 and in humans they are all located on chromosome 9.
  • PRRs pathogen recognition receptors
  • IFN-subtypes have differential capacities to inhibit virus replication. This was shown for several viruses, including HIV, Influenza, Herpes, HCV and HEV 38 ' 42 and reviewed in 29 .
  • the subtype alpha-2 the most widely studied subtype, which is also used in the clinics, is relatively potent in the inhibition of HCV, while it turned out to be relatively weak against HIV 38, 39 .
  • Virus-specific sensitivity is the consequence of differential induction of antiviral ISGs by the different IFN subtypes 43 .
  • SARS CoV-2 susceptible target cells (Vero E6) were pretreated with each of the subtypes of IFN-alpha, or the single IFN-beta subtype.
  • Remdesivir was used as a positive control of inhibition in this system.
  • the results shown in Figure 1 are the mean and SD from triplicate wells.
  • treatment with Remdesivir reduced the amount of viral RNA in the supernatant by more than 3 -log 10.
  • IFN-alpha subtypes displayed different inhibitory potential, with subtypes 8, 10, and 14 exceeding 3-logl0 inhibition, showing high potency.
  • the novelty of the approach proposed here is to take advantage of different IFN-I subtypes to improve both the antiviral effect and to regulate the immune response to limit the excessive production of inflammatory cytokines.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Les coronavirus constituent une famille de virus à ARN simple brin, de sens positif et enveloppés. L'émergence d'un nouveau bêtacoronavirus, le SARS-CoV-2, a conduit à une crise sanitaire majeure associée à une mortalité importante dans les unités de soins intensifs, en raison des complications pulmonaires de la COVID-19. L'objectif principal des inventeurs est d'étudier l'efficacité respective des polypeptides d'IFN-alpha dans la lutte contre la réplication du SARS-CoV-2 et contre la pathogenèse de la maladie à coronavirus 2019 (COVID-19). Ils ont donc testé l'efficacité anti-SARS-CoV-2 de différents sous-types d'IFN-alpha. En particulier, des cellules cibles sensibles au SARS-CoV-2 (Vero E6) ont été prétraitées avec chacun des sous-types d'IFN-alpha, ou avec le sous-type unique d'IFN-bêta. En tant que témoin positif de l'inhibition dans ce système, c'est le remdésivir qui a été utilisé. 24 heures après le traitement, les cellules ont été infectées avec une souche de SARS-CoV-2 pendant 2 heures, les cellules ont ensuite été lavées et des IFN ont été ajoutés à nouveau au milieu de culture. 54 heures plus tard, le virus présent dans le surnageant a été quantifié par extraction d'ARN et une RT-qPCR a été mise en œuvre sur le gène NS14 viral. Les inventeurs ont démontré que certains polypeptides d'IFN-alpha, en particulier les polypeptides d'IFN-alpha 8, 10 ou 14 sont particulièrement appropriés pour inhiber la réplication du virus.
PCT/EP2021/078527 2020-10-15 2021-10-14 Utilisation de polypeptides d'ifn-alpha pour le traitement d'infections à coronavirus WO2022079205A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP20306216 2020-10-15
EP20306216.1 2020-10-15

Publications (1)

Publication Number Publication Date
WO2022079205A1 true WO2022079205A1 (fr) 2022-04-21

Family

ID=73554335

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2021/078527 WO2022079205A1 (fr) 2020-10-15 2021-10-14 Utilisation de polypeptides d'ifn-alpha pour le traitement d'infections à coronavirus

Country Status (1)

Country Link
WO (1) WO2022079205A1 (fr)

Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5382657A (en) 1992-08-26 1995-01-17 Hoffmann-La Roche Inc. Peg-interferon conjugates
US5951974A (en) 1993-11-10 1999-09-14 Enzon, Inc. Interferon polymer conjugates
US5981709A (en) 1997-12-19 1999-11-09 Enzon, Inc. α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same
WO2005023290A2 (fr) * 2003-05-23 2005-03-17 Pestka Biomedical Laboratories, Inc. Utilisation d'interferons pour traiter le syndrome respiratoire aigu severe et d'autres infections virales
US20060051859A1 (en) * 2004-09-09 2006-03-09 Yan Fu Long acting human interferon analogs
WO2006076014A2 (fr) * 2004-04-30 2006-07-20 Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Constructions d'interferon-alpha destinees a etre utilisees dans le traitement du sras
EP1688147A1 (fr) * 1999-09-27 2006-08-09 Coley Pharmaceutical Group, Inc. Procédé utilisant de l'interferon immunostimulatant induit par des acides nucléiques
WO2006111745A2 (fr) * 2005-04-20 2006-10-26 Viragen Incorporated Composition et methode de traitement de l'infection virale
EP1842857A1 (fr) * 2004-11-12 2007-10-10 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Proteines mutantes de l'interferon et leur utilisation
WO2011017160A1 (fr) * 2009-07-28 2011-02-10 Pestka Biomedical Laboratories, Inc. Protéines et gènes d'interférons humains mutant
CN111346219A (zh) * 2020-02-21 2020-06-30 上海甘翼生物医药科技有限公司 干扰素在制备预防冠状病毒感染或预防冠状病毒感染引发的疾病的药物中的用途
CN111374985A (zh) * 2020-02-27 2020-07-07 中国医学科学院医药生物技术研究所 盐酸非那吡啶的医药用途

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5382657A (en) 1992-08-26 1995-01-17 Hoffmann-La Roche Inc. Peg-interferon conjugates
US5951974A (en) 1993-11-10 1999-09-14 Enzon, Inc. Interferon polymer conjugates
US5981709A (en) 1997-12-19 1999-11-09 Enzon, Inc. α-interferon-polymer-conjugates having enhanced biological activity and methods of preparing the same
EP1688147A1 (fr) * 1999-09-27 2006-08-09 Coley Pharmaceutical Group, Inc. Procédé utilisant de l'interferon immunostimulatant induit par des acides nucléiques
WO2005023290A2 (fr) * 2003-05-23 2005-03-17 Pestka Biomedical Laboratories, Inc. Utilisation d'interferons pour traiter le syndrome respiratoire aigu severe et d'autres infections virales
WO2006076014A2 (fr) * 2004-04-30 2006-07-20 Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Constructions d'interferon-alpha destinees a etre utilisees dans le traitement du sras
US20060051859A1 (en) * 2004-09-09 2006-03-09 Yan Fu Long acting human interferon analogs
EP1842857A1 (fr) * 2004-11-12 2007-10-10 Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo Proteines mutantes de l'interferon et leur utilisation
WO2006111745A2 (fr) * 2005-04-20 2006-10-26 Viragen Incorporated Composition et methode de traitement de l'infection virale
WO2011017160A1 (fr) * 2009-07-28 2011-02-10 Pestka Biomedical Laboratories, Inc. Protéines et gènes d'interférons humains mutant
CN111346219A (zh) * 2020-02-21 2020-06-30 上海甘翼生物医药科技有限公司 干扰素在制备预防冠状病毒感染或预防冠状病毒感染引发的疾病的药物中的用途
CN111374985A (zh) * 2020-02-27 2020-07-07 中国医学科学院医药生物技术研究所 盐酸非那吡啶的医药用途

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
"Remington's Pharmaceutical-Sciences", 1980, MACK PUBLISHING CO.
ERWAN SALLARD ET AL: "Type 1 interferons as a potential treatment against COVID-19", ANTIVIRAL RESEARCH, vol. 178, 1 June 2020 (2020-06-01), NL, pages 104791, XP055768812, ISSN: 0166-3542, DOI: 10.1016/j.antiviral.2020.104791 *
GIDEON SCHREIBER: "The Role of Type I Interferons in the Pathogenesis and Treatment of COVID-19", FRONTIERS IN IMMUNOLOGY, vol. 11, 30 September 2020 (2020-09-30), XP055769092, DOI: 10.3389/fimmu.2020.595739 *
H.S. LI ET AL: "Effect of interferon alpha and cyclosporine treatment separately and in combination on Middle East Respiratory Syndrome Coronavirus (MERS-CoV) replication in a human in-vitro and ex-vivo culture model", ANTIVIRAL RESEARCH, vol. 155, 1 July 2018 (2018-07-01), NL, pages 89 - 96, XP055769097, ISSN: 0166-3542, DOI: 10.1016/j.antiviral.2018.05.007 *
HADJADJ J. ET AL.: "Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients", SCIENCE, vol. 369, no. 6504, 7 August 2020 (2020-08-07), pages 718 - 724, XP055769126, DOI: 10.1126/science.abc6027
JEFFY GEORGE ET AL: "Interferon-[alpha] Subtypes As an Adjunct Therapeutic Approach for Human Immunodeficiency Virus Functional Cure", FRONTIERS IN IMMUNOLOGY, vol. 9, 22 February 2018 (2018-02-22), XP055769094, DOI: 10.3389/fimmu.2018.00299 *
K GIBBERT ET AL: "IFN-[alpha] subtypes: distinct biological activities in anti-viral therapy : IFN-[alpha] subtypes in anti-viral therapy", BRITISH JOURNAL OF PHARMACOLOGY, vol. 168, no. 5, 20 February 2013 (2013-02-20), UK, pages 1048 - 1058, XP055768789, ISSN: 0007-1188, DOI: 10.1111/bph.12010 *
MATTHEW PILLAR, EDITOR, BIOPROCESS ONLINE: "ILC Therapeutics' Interferon Alpha 14 Joins The COVID-19 Fight", 5 May 2020 (2020-05-05), XP002801853, Retrieved from the Internet <URL:https://www.bioprocessonline.com/doc/ilc-therapeutics-alpha-interferon-joins-the-covid-fight-0001> [retrieved on 20210127] *
PEREDA R. ET AL., JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2020
SHEAHAN TP ET AL., NAT COMMUN, 2020
TIMOTHY P. SHEAHAN ET AL: "Abstract", NATURE COMMUNICATIONS, vol. 11, no. 1, 10 January 2020 (2020-01-10), XP055769098, DOI: 10.1038/s41467-019-13940-6 *
WANG B. ET AL., BMC INFECTIOUS DISEASES, 2020

Similar Documents

Publication Publication Date Title
JP3246918B2 (ja) 感染症の治療のためのＩＬ―１２およびＩＦＮαの使用
CN1094642A (zh) 治疗组合物
AU2006210753B2 (en) Method and use of interferon compositions for the treatment of avian influenza
US20230079150A1 (en) Methods for prevention or treatment of virus-induced organ injury or failure with il-22 dimer
Schijns et al. Tumour necrosis factor-α, interferon-γ and interferon-β exert antiviral activity in nervous tissue cells
EP4121092B1 (fr) Interferons hybrides pour le traitement d&#39;infections virales
Kern et al. Herpesvirus hominis infection in newborn mice: treatment with interferon inducer polyinosinic-polycytidylic acid
AU2006314497A1 (en) Interferon in influenza
WO2022079205A1 (fr) Utilisation de polypeptides d&#39;ifn-alpha pour le traitement d&#39;infections à coronavirus
US20230181539A1 (en) Methods for the treatment of coronavirus infections
CN1535724B (zh) 重组人干扰素在制备预防严重性急性呼吸道综合征的药物的用途
Higgins et al. Failure to demonstrate synergy between interferon-α and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers
CN1215996A (zh) 减毒的非免疫原性痘病毒和副痘病毒衍生的多功能副痘病毒免疫诱导剂用作药物的新适应症
RU2597150C2 (ru) Противовирусное соединение множественного действия, его состав и способ лечения вирусных заболеваний
Schellekens et al. Oromucosal interferon therapy: relationship between antiviral activity and viral load
US20230277650A1 (en) Use of a birnavirus for the treatment of a disease caused by varicella zoster virus (vzv)
US11883418B2 (en) Compound TSYI-ZAC for inhibiting dengue virus infection and medicinal use thereof
EP3892268A1 (fr) Utilisation de vidofludimus pour le traitement des infections à coronavirus
EP4292604A1 (fr) Méthode d&#39;administration prophylactique contre un virus respiratoire, comprenant l&#39;administration d&#39;interféron bêta à un sujet potentiellement infecté par un virus respiratoire
EA008766B1 (ru) Интерферон-бета при тяжелом остром респираторном синдроме (sars)
WO2022161381A1 (fr) Utilisation d&#39;endostatine dans le traitement et la prévention de maladies associées au coronavirus
KR101876019B1 (ko) 엔-메탄노카르바티미딘을 이용한 대상포진의 치료방법
Seay et al. Interferon treatment of experimental Ross River virus polymyositis
RU2447897C2 (ru) Цитокинсодержащая композиция для лечения вирусных заболеваний
Rollinson et al. Therapy of Aujeszky's disease (pseudorabies) in naturally infected and artificially inoculated piglets using BW B759U (9-[1, 3-dihydroxy-2-propoxymethyl] guanine)

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 21786249

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 21786249

Country of ref document: EP

Kind code of ref document: A1