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

protease inhibitors have been highly effective in curing HCV infection in people. 2 Therefore, it is not surprising that viral protease should also be an attractive target for research on RNA virus infections of animals. Kim et al synthesized peptidyl compounds that target 3C-like proteases (3CLpro) and evaluated them for their efficacy against feline coronavirus (FCoV) and feline calicivirus, as well as important human RNA viruses that encode 3CLpro or related 3C protease. [3] [4] [5] [6] They identified a series of compounds that showed potent inhibitory activity against various coronaviruses, including FCoV, with a wide margin of safety. The in vivo efficacy of their 3CLpro inhibitors was evaluated in mice infected with murine hepatitis virus A59, a murine coronavirus, and found to cause significant reductions in virus titers and pathologic lesions. 5 There are currently no commercially available antiviral drugs for coronavirus infections in people or animals, and the studies of Kim et al showed that, as a proof of principal, inhibition of 3CLpro can lead to suppression of coronavirus replication in vivo. 4, 5 They suggested that some of their 3CLpro inhibitors may be used as therapeutic agents against these important viruses in domestic and wild cats. This was demonstrated to be the case in a subsequent study using experimental feline infectious peritonitis (FIP) virus (FIPV) infection in laboratory cats. 6 Although experimental FIPV infection is highly fatal once the infection reaches a definable stage, 14-20 days of GC376 treatment caused rapid disease remission in six cats that has lasted over 12 months at the time of writing in the remainder.