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

Kyle Rosenke; Atsushi Okumura; Matthew C. Lewis; Friederike Feldmann; Kimberly Meade-White; William F. Bohler; Amanda J. Griffin; Rebecca Rosenke; Carl Shaia; Michael A. Jarvis; Heinz Feldmann

doi:10.1172/jci.insight.160108

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

Kyle Rosenke,¹ Atsushi Okumura,¹ Matthew C. Lewis,¹ Friederike Feldmann,¹ Kimberly Meade-White,¹ William F. Bohler,¹ Amanda J. Griffin,¹ Rebecca Rosenke,² Carl Shaia,² Michael A. Jarvis,³ and Heinz Feldmann¹

Published May 17, 2022 - More info

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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 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.

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

Kyle Rosenke,¹ Atsushi Okumura,¹ Matthew C. Lewis,¹ Friederike Feldmann,¹ Kimberly Meade-White,¹ William F. Bohler,¹ Amanda J. Griffin,¹ Rebecca Rosenke,² Carl Shaia,² Michael A. Jarvis,³ and Heinz Feldmann¹

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

Kyle Rosenke,1 Atsushi Okumura,1 Matthew C. Lewis,1 Friederike Feldmann,1 Kimberly Meade-White,1 William F. Bohler,1 Amanda J. Griffin,1 Rebecca Rosenke,2 Carl Shaia,2 Michael A. Jarvis,3 and Heinz Feldmann1

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Kyle Rosenke,¹ Atsushi Okumura,¹ Matthew C. Lewis,¹ Friederike Feldmann,¹ Kimberly Meade-White,¹ William F. Bohler,¹ Amanda J. Griffin,¹ Rebecca Rosenke,² Carl Shaia,² Michael A. Jarvis,³ and Heinz Feldmann¹