Pathology

Virus

Disease

Coronavirus disease 2019 (COVID-19)

Infectious disease (medical specialty)

Biology

Microbiology

Gene

Molecular biology

Virology

Mutagenesis

Chemistry

Mutation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Genetics

Medicine

Vero cell

The Journal of Infectious Diseases

Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in genomes of RNA viruses during viral replication. β-d-N4-hydroxycytidine (NHC, initial metabolite of molnupiravir) is &amp;gt;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.

β-<scp>d</scp>-<i>N</i>4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells

β-d-N4-hydroxycytidine Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells