ResearchIn-Press PreviewCOVID-19Virology
Open Access | 10.1172/jci.insight.160108
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
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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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Rosenke, R.
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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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Shaia, C.
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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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Published May 17, 2022 - More info
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.