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ResearchIn-Press PreviewCOVID-19Virology Open Access | 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

1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

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1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

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1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

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1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

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1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

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1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

Find articles by Bohler, W. in: JCI | PubMed | Google Scholar

1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

Find articles by Griffin, A. in: JCI | PubMed | Google Scholar

1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

Find articles by Rosenke, R. in: JCI | PubMed | Google Scholar |

1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

Find articles by Shaia, C. in: JCI | PubMed | Google Scholar |

1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

Find articles by Jarvis, M. in: JCI | PubMed | Google Scholar |

1Laboratory of Virology, NIAID, NIH, Hamilton, United States of America

2Rocky Mountain Veterinary Branch, NIAID, NIH, Hamilton, United States of America

3School of Biomedical Sciences, University of Plymouth, Plymouth, United Kingdom

4Laboratory of Virology, NIAID, NIH, Hamilton, Canada

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Published May 17, 2022 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.160108.
Copyright © 2022, Rosenke et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published May 17, 2022 - Version history
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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.

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