Combined Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Reduces Molnupiravir-Induced Mutagenicity and Prevents Selection for Nirmatrelvir/Ritonavir Resistance Mutations

Shuntai Zhou; Nathan Long; Kyle Rosenke; Michael A Jarvis; Heinz Feldmann; Ronald Swanstrom

doi:10.1093/infdis/jiae213

Combined Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 Reduces Molnupiravir-Induced Mutagenicity and Prevents Selection for Nirmatrelvir/Ritonavir Resistance Mutations

J Infect Dis. 2024 Jul 8:jiae213. doi: 10.1093/infdis/jiae213. Online ahead of print.

Authors

Shuntai Zhou^{1

2}, Nathan Long¹, Kyle Rosenke³, Michael A Jarvis^{3

4

5}, Heinz Feldmann³, Ronald Swanstrom^{1

6}

Affiliations

¹ Lineberger Comprehensive Cancer Center.
² Department of Microbiology and Immunology, University of North Carolina at Chapel Hill.
³ Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
⁴ School of Biomedical Sciences, University of Plymouth.
⁵ The Vaccine Group Ltd, Plymouth, Devon, United Kingdom.
⁶ Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill.

PMID: 38973065
DOI: 10.1093/infdis/jiae213

Abstract

We investigated the mutation profiles of severe acute respiratory syndrome coronavirus 2 in samples collected from a molnupiravir and nirmatrelvir/ritonavir combination therapy in macaques. We found that molnupiravir induced several nirmatrelvir resistance mutations at low abundance that were not further selected in combination therapy. Coadministration of nirmatrelvir/ritonavir lowered the magnitude of the mutagenetic effect of molnupiravir.

Keywords: SARS-CoV-2; combination therapy; lethal mutagenesis; molnupiravir; nirmatrelvir.

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Abstract

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