Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model
Syrian hamster study showing efficacy of molnupiravir for multiple variants including omicron.
Concerns have been raised that the mutagenic mechanism of action may create dangerous variants or cause cancer [Hadj Hassine, Swanstrom]. See [Fountain-Jones, Sanderson, ] for analysis of variants potentially created by molnupiravir.
Rosenke et al., 17 May 2022, United Kingdom, peer-reviewed, 11 authors.
Contact:
feldmannh@niaid.nih.gov, michael.jarvis@plymouth.ac.uk.
Abstract: 1
Title: Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model
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Authors: Kyle Rosenke1, Atsushi Okumura1, Matthew C. Lewis1, Friederike Feldmann2,
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Kimberly Meade-White1, W. Forrest Bohler1, Amanda Griffin1, Rebecca Rosenke2, Carl Shaia2,
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Michael A. Jarvis1,3,4*, Heinz Feldmann1*
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Affiliations: 1Laboratory of Virology, 2Rocky Mountain Veterinary Branch, National Institute
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of Allergy and Infectious Diseases, National Institutes of Health; Hamilton, MT, USA; 3School
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of Biomedical Sciences, University of Plymouth; Plymouth, Devon, UK; 4The Vaccine Group
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Ltd; Plymouth, Devon, UK.
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*Corresponding authors: Heinz Feldmann, Rocky Mountain Laboratories, 903 S 4th Street,
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Hamilton, MT, US-59840; Tel: (406)-375-7410; Email: feldmannh@niaid.nih.gov;
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Michael A. Jarvis, University of Plymouth, School of Biomedical Sciences, Derriford Research
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Facility, Plymouth, Devon, UK, PL6 8BU; Tel: +44 (0)1752-437444; Email:
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michael.jarvis@plymouth.ac.uk
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One Sentence Summary: MK-4482 inhibits replication of multiple SARS-CoV-2 variants of
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concern, including Omicron, in the Syrian hamster COVID-19 model
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Conflict of Interest Statement: The authors have declared that no conflict of interest exists.
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ABSTRACT
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The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC) containing a
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heavily mutated spike protein capable of escaping preexisting immunity identifies a continued
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need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside
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analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently
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approved for SARS-CoV-2 infections in high-risk adults. Here we assessed the efficacy of MK-
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4482 against the earlier Alpha, Beta and Delta VOCs and Omicron in the hamster COVID-19
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model. Omicron replication and associated lung disease in vehicle treated hamsters was reduced
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compared to the earlier VOCs. MK-4482 treatment inhibited virus replication in the lungs of
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Alpha, Beta and Delta VOC infected hamsters. Importantly, MK-4482 profoundly inhibited virus
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replication in the upper and lower respiratory tract of hamsters infected with the Omicron VOC.
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Consistent with its mutagenic mechanism, MK-4482 treatment had a more pronounced inhibitory
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effect on infectious titers compared to viral RNA genome load. Histopathologic analysis showed
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that MK-4482 treatment caused a concomitant reduction in the level of lung disease and viral
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antigen load in infected hamsters across all VOCs examined. Together, our data indicate the
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potential of MK-4482 as an effective antiviral against known SARS-CoV-2 VOCs, especially
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Omicron, and likely future SARS-CoV-2 variants.
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