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

There were certain forms of FIP that appeared to influence treatment success. The behavior of GC376 treatment in treating ocular FIP was paradoxical as it responded extremely well to GC376. Even though ocular lesions responded to treatment, all of the three cats with eye involvement ultimately succumbed to brain disease, thus supporting the close anatomic relationship of the eye and the CNS. Chronic ileocecal and colon involvement and stunted growth in older cats also carried a bad prognosis in this study. A number of these cats appeared to develop abdominal effusions only as a terminal manifestation of their disease. Host factors also associated with reduced response to antiviral treatment in other viral infections, such as HCV, include age, sex, liver cirrhosis or fibrosis, race or body weight. 24 Emergence of resistance is a major concern for any antiviral drug, but FIPV is rarely transmitted from cat to cat, 13, 14 and drug resistance, if it does occur, would only be a problem for individual treated cats and not the entire population. Although viral resistance to GC376 was not observed in up to 20 passages in vitro, 6 suggesting that resistance is not easily acquired, long-term and repetitive treatment in vivo may be a stronger selection factor. However, viral resistance did not appear to be responsible for relapses of abdominal diseases in five treated cats. These cats had granulomatous-like masses, often in the colon and ileo-cecal-colic lymph nodes, which may have provided a protected place for viruses to persist. Protection of pathogens within granulomas is a well-documented phenomenon for mycobacteria and applies to other pathogens such as viruses. 24 The status of liver disease (cirrhosis) in HCV infection also increases the risk of relapse and necessitates longer treatment, indicating that viruses may also be protected from drugs when in certain protected sites. 2 The formation of 'protective granulomas' involves a large number of chemokines and cytokines and upregulation of chemokine receptors, addressins, selectins and integrins. 25 Persistence of pathogens in such protected sites may require a higher dose of drug and a longer treatment period.