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Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model

Rosenke et al., JCI Insight, doi:10.1172/jci.insight.160108
May 2022  
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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 Chamod, Gruber, Hadj Hassine, Huntsman, Marikawa, Swanstrom, Waters, Zhou, Zibat. Multiple analyses have identified variants potentially created by molnupiravir Fountain-Jones, Kosakovsky Pond, Sanderson,
Rosenke et al., 17 May 2022, United Kingdom, peer-reviewed, 11 authors. Contact:,
This PaperMolnupiravirAll
Molnupiravir inhibits SARS-CoV-2 variants including Omicron in the hamster model
Kyle Rosenke, Atsushi Okumura, Matthew C Lewis, Friederike Feldmann, Kimberly Meade-White, W Forrest Bohler, Amanda Griffin, Rebecca Rosenke, Carl Shaia, Michael A Jarvis, Heinz Feldmann
The recent emergence of the SARS-CoV-2 Omicron variant of concern (VOC) containing a heavily mutated spike protein capable of escaping preexisting immunity identifies a continued need for interventional measures. Molnupiravir (MK-4482), an orally administered nucleoside analog, has demonstrated efficacy against earlier SARS-CoV-2 lineages and was recently approved for SARS-CoV-2 infections in high-risk adults. Here we assessed the efficacy of MK-4482 against the earlier Alpha, Beta and Delta VOCs and Omicron in the hamster COVID-19 model. Omicron replication and associated lung disease in vehicle treated hamsters was reduced compared to the earlier VOCs. MK-4482 treatment inhibited virus replication in the lungs of Alpha, Beta and Delta VOC infected hamsters. Importantly, MK-4482 profoundly inhibited virus replication in the upper and lower respiratory tract of hamsters infected with the Omicron VOC. Consistent with its mutagenic mechanism, MK-4482 treatment had a more pronounced inhibitory effect on infectious titers compared to viral RNA genome load. Histopathologic analysis showed that MK-4482 treatment caused a concomitant reduction in the level of lung disease and viral antigen load in infected hamsters across all VOCs examined. Together, our data indicate the potential of MK-4482 as an effective antiviral against known SARS-CoV-2 VOCs, especially Omicron, and likely future SARS-CoV-2 variants.
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