Preclinical evaluation of AT-527, a novel guanosine nucleotide prodrug with potent, pan-genotypic activity against hepatitis C virus.

ABSTRACT: Despite the availability of highly effective direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) infections, sustained viral response (SVR) rates remain suboptimal for difficult-to-treat patient populations such as those with HCV genotype 3, cirrhosis or prior treatment experience, warranting development of more potent HCV replication antivirals. AT-527 is the hemi-sulfate salt of AT-511, a novel phosphoramidate prodrug of 2'-fluoro-2'-C-methylguanosine-5'-monophosphate that has potent in vitro activity against HCV. The EC50 of AT-511, determined using HCV laboratory strains and clinical isolates with genotypes 1-5, ranged from 5-28 nM. The active 5'-triphosphate metabolite, AT-9010, specifically inhibited the HCV RNA-dependent RNA polymerase. AT-511 did not

SUBMITTER: Good SS 

PROVIDER: S-EPMC6949113 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature