DNA-dependent RNA polymerase Incorporates β-D-N4-hydroxycytidine (NHC) Linking Molnupiravir to Host Transcription-Dependent Mutagenesis

Molnupiravir, a prodrug of β-D-N⁴-hydroxycytidine (NHC), is an antiviral RNA mutagen that is incorporated by viral RNA-dependent RNA polymerases (RdRp) during replication of viral RNA genomes, ultimately driving target viruses such as SARS-CoV-2 toward lethal mutagenesis. In this study, first, we biochemically tested whether DNA-dependent RNA polymerases (DdRps) including T7 RNA polymerase and host RNA polymerase II, can also incorporate NHC-triphosphate (NHC-TP) during RNA synthesis