Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 224, Issue 3, Pages 415-419Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab247
Keywords
molnupiravir; mutagenicity; NHC; SARS-CoV-2
Categories
Funding
- National Institutes of Health Antiviral Drug Discovery and Development Center [U19 AI142759]
- National Institutes of Health [R01 AI141327, R01 AI140970]
- UNC Center for AIDS Research (National Institutes of Health) [P30 AI50410]
- UNC Lineberger Comprehensive Cancer Center (National Institutes of Health) [P30 CA16068]
- Emory University Center for AIDS Research (National Institutes of Health) [P30 AI050409]
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Mutagenic ribonucleosides can serve as broad-spectrum antiviral agents, but may pose risks to the host due to their host mutagenic activity in addition to antiviral activity.
Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside tri-phosphate form and concentrate in genomes of RNA viruses during viral replication. beta-D-N-4-hydroxycridine (NHC, initial metabolite of molnupiravir) is >100-fold more active than ribavirin or favipiravir against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate highly active mutagenic ribonucleosides may hold risk for the host.
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