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Discovery of the first up-and-coming deuterated oral SARS-CoV-2 RdRp covalent candidate VV116. (a) Medicinal chemistry efforts led to discovery of the first deuterated oral RdRp candidate, VV116. (b) Important milestones in VV116 discovery from natural nucleosides to VV116. (c) Proposed mechanism of action of the tri-isobutyrate ester prodrug VV116 against SARS-CoV-2. SARS-CoV-2 RNA replication was blocked by the active metabolite VV116-NMP through formation of a covalent bond.
