Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model

DOI record: { "DOI": "10.1093/infdis/jiab361", "ISSN": [ "0022-1899", "1537-6613" ], "URL": "http://dx.doi.org/10.1093/infdis/jiab361", "abstract": "<jats:title>Abstract</jats:title><jats:p>The emergence of SARS-CoV-2 variants of concern (VoCs) has exacerbated the COVID-19 pandemic. Currently available monoclonal antibodies and vaccines appear to have reduced efficacy against some of these VoCs. Antivirals targeting conserved proteins of SARS-CoV-2 are unlikely to be affected by mutations arising in VoCs and should therefore be effective against emerging variants. We here investigate the efficacy of molnupiravir, currently in phase 2 clinical trials, in hamsters infected with Wuhan strain or B.1.1.7 and B.1.351 variants. Molnupiravir proved to be effective against infections with each of the variants and therefore may have potential combating current and future emerging VoCs.</jats:p>", "author": [ { "affiliation": [ { "name": "Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium" } ], "family": "Abdelnabi", "given": "Rana", "sequence": "first" }, { "affiliation": [ { "name": "Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium" } ], "family": "Foo", "given": "Caroline S", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium" } ], "family": "De Jonghe", "given": "Steven", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-9118-8608", "affiliation": [ { "name": "Laboratory of Clinical and Epidemiological Virology, Department of Microbiology, Immunology and Transplantation, Rega Institute, Katholieke Universiteit Leuven, Leuven, Belgium" }, { "name": "Zoonotic Infectious Diseases Unit, KU Leuven, Leuven, Belgium" } ], "authenticated-orcid": false, "family": "Maes", "given": "Piet", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Imaging and Pathology, Division of Translational Cell and Tissue Research, Katholieke Universiteit Leuven, Leuven, Belgium" } ], "family": "Weynand", "given": "Birgit", "sequence": "additional" }, { "affiliation": [ { "name": "Laboratory of Virology and Chemotherapy, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium" }, { "name": "Global Virus Network, Baltimore, Maryland, USA" } ], "family": "Neyts", "given": "Johan", "sequence": "additional" } ], "container-title": "The Journal of Infectious Diseases", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2021, 7, 8 ] ], "date-time": "2021-07-08T19:13:00Z", "timestamp": 1625771580000 }, "deposited": { "date-parts": [ [ 2023, 1, 3 ] ], "date-time": "2023-01-03T11:35:22Z", "timestamp": 1672745722000 }, "funder": [ { "DOI": "10.13039/501100004040", "doi-asserted-by": "publisher", "name": "Katholieke Universiteit Leuven" }, { "DOI": "10.13039/501100010648", "doi-asserted-by": "crossref", "name": "Universitair Ziekenhuis Leuven" }, { "DOI": "10.13039/501100003130", "award": [ "G0G4820N" ], "doi-asserted-by": "publisher", "name": "Fonds Wetenschappelijk Onderzoek" }, { "DOI": "10.13039/501100000780", "award": [ "101003627" ], "doi-asserted-by": "publisher", "name": "European Union" }, { "DOI": "10.13039/100000865", "award": [ "INV-00636" ], "doi-asserted-by": "publisher", "name": "Bill and Melinda Gates Foundation" } ], "indexed": { "date-parts": [ [ 2024, 5, 12 ] ], "date-time": "2024-05-12T01:11:23Z", "timestamp": 1715476283292 }, "is-referenced-by-count": 99, "issue": "5", "issued": { "date-parts": [ [ 2021, 7, 9 ] ] }, "journal-issue": { "issue": "5", "published-online": { "date-parts": [ [ 2021, 7, 9 ] ] }, "published-print": { "date-parts": [ [ 2021, 9, 1 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2021, 7, 9 ] ], "date-time": "2021-07-09T00:00:00Z", "timestamp": 1625788800000 } } ], "link": [ { "URL": "http://academic.oup.com/jid/advance-article-pdf/doi/10.1093/infdis/jiab361/39721682/jiab361.pdf", "content-type": "application/pdf", "content-version": "am", "intended-application": "syndication" }, { "URL": "http://academic.oup.com/jid/article-pdf/224/5/749/40166589/jiab361.pdf", "content-type": "application/pdf", "content-version": "vor", "intended-application": "syndication" }, { "URL": "http://academic.oup.com/jid/article-pdf/224/5/749/40166589/jiab361.pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "286", "original-title": [], "page": "749-753", "prefix": "10.1093", "published": { "date-parts": [ [ 2021, 7, 9 ] ] }, "published-online": { "date-parts": [ [ 2021, 7, 9 ] ] }, "published-other": { "date-parts": [ [ 2021, 9, 1 ] ] }, "published-print": { "date-parts": [ [ 2021, 9, 1 ] ] }, "publisher": "Oxford University Press (OUP)", "reference": [ { "DOI": "10.1056/NEJMoa2001017", "article-title": "A novel coronavirus from patients with pneumonia in China, 2019", "author": "Zhu", "doi-asserted-by": "crossref", "first-page": "727", "journal-title": "N Engl J Med", "key": "2021090109221259500_CIT0001", "volume": "382", "year": "2020" }, { "DOI": "10.1016/j.chom.2021.02.020", "article-title": "The variant gambit: COVID-19’s next move", "author": "Plante", "doi-asserted-by": "crossref", "first-page": "508", "journal-title": "Cell Host Microbe", "key": "2021090109221259500_CIT0002", "volume": "29", "year": "2021" }, { "DOI": "10.1016/S0140-6736(21)00183-5", "article-title": "Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence", "author": "Sabino", "doi-asserted-by": "crossref", "first-page": "452", "journal-title": "Lancet", "key": "2021090109221259500_CIT0003", "volume": "397", "year": "2021" }, { "DOI": "10.1136/bmj.n359", "article-title": "Covid-19: the E484K mutation and the risks it poses", "author": "Wise", "doi-asserted-by": "crossref", "first-page": "n359", "journal-title": "BMJ", "key": "2021090109221259500_CIT0004", "volume": "372", "year": "2021" }, { "DOI": "10.1128/JVI.01965-17", "article-title": "β-d-N4-hydroxycytidine is a potent anti-alphavirus compound that induces a high level of mutations in the viral genome", "author": "Urakova", "doi-asserted-by": "crossref", "first-page": "e01965-17", "journal-title": "J Virol", "key": "2021090109221259500_CIT0005", "volume": "92", "year": "2017" }, { "DOI": "10.1126/scitranslmed.aax5866", "article-title": "Characterization of orally efficacious influenza drug with high resistance barrier in ferrets and human airway epithelia", "author": "Toots", "doi-asserted-by": "crossref", "first-page": "eaax5866", "journal-title": "Sci Transl Med", "key": "2021090109221259500_CIT0006", "volume": "11", "year": "2019" }, { "article-title": "The combined treatment of molnupiravir and favipiravir results in a marked potentiation of antiviral efficacy in a SARS-CoV-2 hamster infection model", "author": "Abdelnabi", "journal-title": "bioRxiv", "key": "2021090109221259500_CIT0007", "year": "10" }, { "DOI": "10.1038/s41586-021-03312-w", "article-title": "SARS-CoV-2 infection is effectively treated and prevented by EIDD-2801", "author": "Wahl", "doi-asserted-by": "crossref", "journal-title": "Nature", "key": "2021090109221259500_CIT0008", "year": "2021" }, { "DOI": "10.1038/s41564-020-00835-2", "article-title": "Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets", "author": "Cox", "doi-asserted-by": "crossref", "first-page": "11", "journal-title": "Nat Microbiol", "key": "2021090109221259500_CIT0009", "volume": "6", "year": "2021" }, { "DOI": "10.1128/AAC.02428-20", "article-title": "Human safety, tolerability, and pharmacokinetics of molnupiravir, a novel broad-spectrum oral antiviral agent with activity against SARS-CoV-2", "author": "Painter", "doi-asserted-by": "crossref", "first-page": "e02428-20", "journal-title": "Antimicrob Agents Chemother", "key": "2021090109221259500_CIT0010", "volume": "65", "year": "2021" }, { "article-title": "Reduction in infectious SARS-CoV-2 in treatment study of COVID-19 with molnupiravir", "author": "Painter", "key": "2021090109221259500_CIT0011" }, { "DOI": "10.1016/j.ebiom.2021.103403", "article-title": "Comparing infectivity and virulence of emerging SARS-CoV-2 variants in Syrian hamsters", "author": "Abdelnabi", "doi-asserted-by": "crossref", "first-page": "103403", "journal-title": "EBioMedicine", "key": "2021090109221259500_CIT0012", "volume": "68", "year": "2021" }, { "DOI": "10.1038/s41586-021-03398-2", "article-title": "Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7", "author": "Wang", "doi-asserted-by": "crossref", "first-page": "130", "journal-title": "Nature", "key": "2021090109221259500_CIT0013", "volume": "593", "year": "2021" }, { "DOI": "10.1126/science.371.6527.329", "article-title": "New mutations raise specter of ‘immune escape’", "author": "Kupferschmidt", "doi-asserted-by": "crossref", "first-page": "329", "journal-title": "Science", "key": "2021090109221259500_CIT0014", "volume": "371", "year": "2021" }, { "DOI": "10.1016/j.coviro.2021.03.010", "article-title": "Structure and function of SARS-CoV-2 polymerase", "author": "Hillen", "doi-asserted-by": "crossref", "first-page": "82", "journal-title": "Curr Opin Virol", "key": "2021090109221259500_CIT0015", "volume": "48", "year": "2021" } ], "reference-count": 15, "references-count": 15, "relation": {}, "resource": { "primary": { "URL": "https://academic.oup.com/jid/article/224/5/749/6318434" } }, "score": 1, "short-title": [], "source": "Crossref", "subject": [], "subtitle": [], "title": "Molnupiravir Inhibits Replication of the Emerging SARS-CoV-2 Variants of Concern in a Hamster Infection Model", "type": "journal-article", "volume": "224" }