Molnupiravir (MK-4482) is efficacious against Omicron and other SARS-CoV-2 variants in the Syrian hamster COVID-19 model

Rosenke, K.; Okumura, A.; Lewis, M. C.; Feldmann, F.; Meade-White, K.; Bohler, W. F.; Griffin, A.; Rosenke, R.; Shaia, C.; Jarvis, M.; Feldmann, H.

doi:10.1101/2022.02.22.481491

bioRxiv · 10.1101/2022.02.22.481491

Molnupiravir (MK-4482) is efficacious against Omicron and other SARS-CoV-2 variants in the Syrian hamster COVID-19 model

Rosenke, K.·Okumura, A.·Lewis, M. C.·Feldmann, F.·Meade-White, K.·Bohler, W. F.·Griffin, A.·Rosenke, R.·Shaia, C.·Jarvis, M.·Feldmann, H.

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Abstract

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 Syrian 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 virus 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. One Sentence SummaryMK-4482 inhibits replication of multiple SARS-CoV-2 variants of concern, including Omicron, in the Syrian hamster COVID-19 model

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Rosenke, K., Okumura, A., Lewis, M. C., Feldmann, F., Meade-White, K., Bohler, W. F., Griffin, A., Rosenke, R., Shaia, C., Jarvis, M., Feldmann, H.. 2022-02-24. Molnupiravir (MK-4482) is efficacious against Omicron and other SARS-CoV-2 variants in the Syrian hamster COVID-19 model. https://doi.org/10.1101/2022.02.22.481491

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