VV-116 (also known as VV116, JT-001) is a novel, potent and orally administered anti-SARS-CoV-2 nucleoside drug candidate (IC50 = 0.67±0.24 μM) acting as a viral RNA-dependent RNA polymerase (RdRp) inhibitor and is under investigation for COVID-19 treatment in China. As of Jun 27th 2022, the developer of this drug (Junshi Biosciences and Vigonvita) has submitted an NDA to China FDA. VV-116 is essentially an analog of remdesivir or GS-441524, as it has to be converted to the mono-deuterated form of GS-441524 in vivo, followed by a triphosphorylation to form the active metabolite which is the same as that of remdesivir except for the deuterium atom at the 5-position of triazine-pyrrole fused ring system. As a mono-deuterated, tri-isobutyrate ester prodrug of the RDV parent nucleoside, VV116 is rapidly metabolized into the parent nucleoside (116-N1) in vivo. 116-N1 is intracellularly converted to the nucleoside triphosphate active form, which would interfere with the function of RNA-dependent RNA polymerase of SARS-CoV-2, thus exerting antiviral effects. VV116 showed potent activity against a panel of SARS-CoV-2 variants (alpha, beta, delta, and omicron) and excellent therapeutic efficacy in the mice model. This prodrug was endowed with significantly improved oral absorption and a favorable tissue distribution profile, circumventing the liver-targeting issue of the phosphoramidate prodrugs.