An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses

In Vitro and hamster study of drug associated SARS-CoV-2 mutations with several drugs including molnupiravir and favipiravir. Next-generation sequencing was used to identify de novo mutational spectra and single base substitution mutational signatures. The study also assessed viral replication kinetics and immune responses using VeroE6-TMPRSS2 and Calu-3 cell models, and compared the pathogenicity of the mutated viruses in vivo in hamsters. Favipiravir showed high increase in nucleotide diversity and was associated with eleveted C>T mutations. Molnupiravir treatment led to elevated C>T and A>G mutations, with some mutated viruses forming significantly larger plaques and inducing stronger proinflammatory responses, raising concerns about the potential emergence of more dangerous strains with use of molnupiravir.