Bemnifosbuvir (AT-511), a novel phosphoramidate prodrug of 2'-fluoro-2'-C-methylguanosine-5'-monophosphate, exhibits potent in vitro activity against HCV.

HCV:5-28 nM (EC50), SARS-CoV-2:0.47 μM (EC90)

Bemnifosbuvir is a novel phosphoramidate prodrug of 2'-fluoro-2'-C-methylguanosine-5'-monophosphate that has potent in vitro activity against HCV[1].In the absence of cells, Bemnifosbuvir was stable when incubated in culture medium at 37°C for up to 24 h. AT-9010 was the predominant intracellular metabolite measured in all hepatocyte species and Huh-7 cell incubations with 10 μM Bemnifosbuvir and, except in mouse hepatocytes,far exceeded intracellular Bemnifosbuvir concentrations,demonstrating that the active TP was efficiently formed from its phosphoramidate protide in liver cells. In hepatocyte incubations, the relative levels of AT-9010 formed, and its accumulation over 24 h expressed as area under the curve or AUC0-24h; from most to least abundant, were rat>human >mouse >dog/monkey.

Treatment with moxifloxacin every 8hr was accompanied by longer survival than in any other group.Tissue cultures 30hr after bacterial challenge showed considerably less bacterial growth in the spleens and lungs of moxifloxacin-treated animals than in the other groups, but not in their livers[2].