GS-441524

Uses

GS 441524 Triphosphate is known to strongly inhibit feline peritonitis which is a highly lethal coronavirus disease in cats. Also useful in the potential treatment of ebola and emerging viruses.

Application

GS-441524 is a nucleoside analogue antiviral drug which was developed by Gilead Sciences. It is the main plasma metabolite of the antiviral prodrug remdesivir, and has a half-life of around 24 hours in human patients. Remdesivir and GS-441524 were both found to be effective in vitro against feline coronavirus strains responsible for feline infectious peritonitis (FIP), a lethal systemic disease affecting domestic cats. Remdesivir was never tested in cats (though some vets now offer it), but GS-441524 has been found to be effective treatment for FIP and is widely used despite no official FDA approval due to Gilead's refusal to license this drug for veterinary use.

Definition

ChEBI: GS-443902 is an organic triphosphate that is GS-441524 in which the 5'-hydroxy group has been replaced by a triphosphate group. It is the active metabolite of remdesivir. It has a role as a drug metabolite, an antiviral drug and an anticoronaviral agent. It is a C-nucleoside, an aromatic amine, a nitrile, a pyrrolotriazine and an organic triphosphate. It is functionally related to a GS-441524.

Advantages

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. Specific advantages cited include ease of synthesis, lower kidney and hepatotoxicity, as well as potential for oral delivery (which is precluded of remdesivir because of poor hepatic stability and first pass metabolism). The public health advocacy group, Public Citizen, in an open letter urged the DHHS and Gilead to investigate GS-441524 for the treatment of COVID-19, suggesting that GILEAD was not doing so for financial motives related to the longer intellectual property lifespan of Remdesivir. Direct efficacy against SARS-CoV-2 was demonstrated in a mouse model of COVID-19. A deuterium modified version of GS-441524 has been produced and has shown pre-clinical efficacy in both cell culture and mouse models by a team including members of Wuhan Institute of Virology.