Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis

Pedersen, Niels C; Kim, Yunjeong; Liu, Hongwei; Galasiti Kankanamalage, Anushka C; Eckstrand, Chrissy; Groutas, William C; Bannasch, Michael; Meadows, Juliana M; Chang, Kyeong-Ok

Success with GC376 treatment against experimental FIPV infection prompted us to investigate whether GC376 could be equally efficacious against naturally occurring FIP. 6 There are significant differences between experimental effusive abdominal FIP and the naturally occurring disease. Experimental disease bypasses the critical early stage that starts as kittens with exposure to an innocuous feline enteric coronavirus (FECV). 12 Naturally occurring FIP results from specific mutants that arise following FECV infection and FIP occurs in the presence of FECV immunity. 13, 14 Experimental FIP, in contrast, is induced in coronavirus naïve cats by an intraperitoneal injection of a large dose of laboratory catpassaged and purified FIPV. Naturally occurring disease is often subclinical for many weeks or months before outward signs of disease are observed, whereas experimental disease signs appear within 2-4 weeks and rapidly progresses. Naturally occurring FIP presents in a variety of clinical forms, whereas the experimental infection is almost always effusive and abdominal. FIP in nature is also affected by a milieu of disease enhancing cofactors, while experimental disease occurs in cats that are free of such extraneous influences. 15 Differences may explain why a small proportion of cats naturally exposed to FIPVs develop disease, whereas 80-100% of experimentally infected cats die. 15, 16 Our predictions proved correct and naturally occurring FIP was much more difficult to treat than the experimental disease. It must be stressed, however, that this trial would not have been approved without the information obtained from pharmacokinetic, acute and chronic toxicity, and efficacy studies conducted on laboratory cats.