An investigational study into the drug-associated mutational signature in SARS-CoV-2 viruses
, C., The University of Hong Kong, PhD Thesis, Jul 2024
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.
Potential risks of molnupiravir include the creation of dangerous variants, and mutagenicity, carcinogenicity, teratogenicity, and embryotoxicity1-15. Multiple analyses have identified variants potentially created by molnupiravir16-20.
Study covers molnupiravir and favipiravir.
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Shum et al., 30 Jul 2024, preprint, 1 author.