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Mechanism of molnupiravir-induced SARS-CoV-2 mutagenesis

2021; Nature Portfolio; Volume: 28; Issue: 9 Linguagem: Inglês

10.1038/s41594-021-00651-0

1545-9993

Florian Kabinger, Carina Stiller, Jana Schmitzová, Christian Dienemann, Goran Kokić, Hauke S. Hillen, Claudia Höbartner, Patrick Cramer,

Animal Virus Infections Studies

Molnupiravir is an orally available antiviral drug candidate currently in phase III trials for the treatment of patients with COVID-19. Molnupiravir increases the frequency of viral RNA mutations and impairs SARS-CoV-2 replication in animal models and in humans. Here, we establish the molecular mechanisms underlying molnupiravir-induced RNA mutagenesis by the viral RNA-dependent RNA polymerase (RdRp). Biochemical assays show that the RdRp uses the active form of molnupiravir, β-D-N