GS-704277

Description: GS-704277 is a phase II alanine conjugated metabolite of Remdesivir. Remdesivir is an investigational drug, is highly effective in combating 2019-nCoV (COVID-19 pandemic, CoronaVirus) infections in vitro. It has EC50s of 74 nM for ARS-CoV and MERS-CoV in HAE cells, and 30 nM for murine hepatitis virus in delayed brain tumor cells. GS-5734 potently inhibits CoVs with intact proofreading. Following selection with the GS-5734 parent nucleoside, 2 amino acid substitutions in the nsp12 polymerase at residues that are identical across CoVs provide low-level resistance to GS-5734. The resistance mutations decrease viral fitness of MHV in vitro and attenuate pathogenesis in a SARS-CoV animal model of infection. Together, these studies define the target of GS-5734 activity and demonstrate that resistance is difficult to select, only partial, and impairs fitness and virulence of MHV and SARS-CoV, supporting further development of GS-5734 as a potential effective pan-CoV antiviral.

References:

1. EastmanRT, et al. Remdesivir: A Review of Its Discovery and DevelopmentLeading to Emergency Use Authorization for Treatment of COVID-19published correction appears in ACS Cent Sci. 2020 Jun 24; 6(6):1009.ACS Cent Sci. 2020; 6(5):672-683.

2. WangM, et al. Remdesivir and chloroquine effectively inhibit the recentlyemerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020Mar; 30(3):269-271.

3. MBio. 2018 Mar 6; 9(2). pii: e00221-18.

Related CAS#: 1355149-45-9 GS443902 (GS-441524 triphosphate); 1809249-37-3 (Remdesivir); 1191237-69-0 (GS-441524, an active metabolite of Remdesivir); 1191237-80-5(Remdesivir O-desphosphate acetonide impurity); 1911578-74-9(Remdesivir nucleoside monophosphate); 1911579-04-8 (GS-704277)