Feline infectious peritonitis (FIP) is a common and highly fatal coronavirus disease in domestic cats. Recent studies of diseases caused by several RNA viruses in humans and other species suggest that antiviral treatments may be effective against FIP in cats. The small molecule nucleoside analog GS-441524 is a molecular precursor of pharmacologically active nucleoside triphosphate molecules. These analogs act as alternative substrates and RNA chain terminators for viral RNA-dependent RNA polymerases. We determined that GS-441524 is nontoxic to feline cells at concentrations up to 100 uM and effectively inhibits FIPV replication in cultured CRFK cells and naturally infected feline peritoneal macrophages at concentrations as low as 1 uM. We determined the pharmacokinetics of GS-441524 in cats and determined the dose that maintains effective blood concentrations for 24 hours. In experimental FIPV infections in cats, treatment with GS-441524 resulted in rapid reversal of disease symptoms and return to normal in 10/10 cats in just two weeks, with no apparent toxicity.
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