VV116 Chemical Properties

Density 

1.375±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

solubility 

DMF: 20 mg/ml; DMSO: 12 mg/ml; Ethanol: Slightly soluble

form 

A solid

pka

4.110±0.30(predicted)

color 

White to off-white

InChIKey

RVSSLHFYCSUAHY-QXMJNOOVSA-N

SMILES

C([C@@]1(C2=CC([2H])=C3C(=NC=NN23)N)O[C@@H]([C@H]([C@H]1OC(=O)C(C)C)OC(=O)C(C)C)COC(=O)C(C)C)#N

VV116 Usage And Synthesis

Description

VV116, also known as JT001, is an oral drug candidate of nucleoside analog against SARS-CoV-2. VV116 is a deuterated, tri-isobutyrate ester prodrug of the RDV parent nucleoside, and is rapidly metabolized into the parent nucleoside (116-N1) in the body. 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 (Fig. 1). 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.

Uses

GS-621763-d1 is the deuterium labeled GS-621763 (HY-145119)[1]. GS-621763, an orally bioavailable proagent of GS-441524, shows antiviral activity against SARS-CoV-2 pathogenesis in mice[2].

References

[1] Russak EM, et al. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019 Feb;53(2):211-216. DOI:10.1177/1060028018797110
[2] Sch?fer A, et al. Therapeutic efficacy of an oral nucleoside analog of remdesivir against SARS-CoV-2 pathogenesis in mice. bioRxiv [Preprint]. 2021 Sep 17:2021.09.13.460111. DOI:10.1101/2021.09.13.460111