GS-441524


GS-441524 is an antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, which has a half-life of around 24 hours in human patients. GS-441524 nucleoside is phosphorylated by nucleoside kinases, and then phosphorylated again by nucleoside-diphosphate kinase to the active nucleotide triphosphate form. Remdesivir and GS-441524 were both tested against FIP in cell culture and found to be equivalent. Remdesivir was never tested in cats but GS-441524 has been found exceptionally active against feline infectious peritonitis, a lethal coronavirus disease which affects domestic cats and is widely used despite no official FDA approval due to Gilead's refusal to license this drug for veterinary use. GS-441524 is either similar to or more potent than remdesivir against SARS-CoV-2 in cell culture, with some researchers arguing that GS-441524 would be better than remdesivir for the treatment of COVID-19.

Use

Since FIP is usually fatal and there are no approved treatments available, GS-441524 has reportedly been sold on the black market and used by pet owners to treat affected cats, although Gilead Sciences has refused to license the drug for veterinary use. Its efficacy for this purpose has been conclusively demonstrated in multiple trials, including field trials.
GS-441524 is the nucleoside of the prodrug remdesivir. It is remdesivir's predominant metabolite circulating in the serum due to rapid hydrolysis followed by dephosphorylation. Some researchers have suggested its utility as a treatment for COVID-19 and pointed out advantages over Remdesivir, including lack of on-target liver toxicity and much cheaper and simpler synthesis.