Remdesivir O-desphosphate acetonide impurity is a Remdesivir impurity and an important intermediate to synthesize antiviral drug remdesivir. Remdesivir (GS-5734), a nucleoside analogue with effective antiviral activity and is highly effective in the control of SARS-CoV-2 (COVID-19) infection in vitro. Remdesivir (GS-5734; Veklury) is an FDA approved drug for the treatment of 2019-nCoV (COVID-19 pandemic, CoronaVirus) infections requiring hospitalization. Veklury (approved on Oct 22, 2020) is the first treatment for COVID-19 to receive FDA approval. 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.

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CAS：1191237-80-5