Journal Scan: A promising contender for fighting FIP
Feline infectious peritonitis (FIP) is one of the most common infectious causes of death in young cats. FIP is caused by a mutation of normal feline enteric coronavirus into the highly pathogenic feline infectious peritonitis virus. This mutation occurs only in certain cats, and there is no current method to predict which cats will suffer from the effects of the mutated virus. The infection results in granulomatous lesions that can be distributed throughout the body, with or without thoracic or abdominal effusion. The progression is rapidly progressive and virtually always fatal. There is currently no effective treatment for FIP.
The challenger enters the ring
A recent study investigated the pharmacokinetics, safety and efficacy of a novel coronavirus inhibitory compound. The compound targets the virus’s 3C-like protease (3CLpro) that is involved in viral replication. This is especially significant since the FIP virus shares this with other significant human coronaviruses such as the severe acute respiratory distress syndrome (SARS) and Middle East respiratory syndrome (MERS) viruses.
Round one—pharmacokinetics. The authors first determined the pharmacokinetics of the 3CLpro inhibitor. Two healthy specific-pathogen-free (SPF) cats aged 6 to 9 months were each given single subcutaneous doses of the compound, and serial blood samples were taken every four hours for two days. The compound was found to be rapidly absorbed after subcutaneous injection, and ideal dosing was determined to be twice daily.
Round two—safety. The authors next determined whether the drug was safe for regular dosing. Four healthy SPF cats were each given twice daily subcutaneous injections of the compound for four weeks. The cats were examined daily, and blood was taken weekly for a complete blood count and serum chemistry profile. No clinically significant changes were noticed in any of the cats during the four weeks.
Round three—efficacy. Having determined the compound’s safety and pharmacokinetics, the authors then wanted to determine whether it would be effective against experimentally induced FIP. Eight healthy 8- to 10-month-old SPF cats were inoculated intraperitoneally with experimentally induced FIP virus. Treatment with the 3CLpro inhibitor was begun for four of the cats after they developed fever, jaundice, weight loss and lymphopenia. These cats had no or only mild ascites. The other four cats were allowed to progress to develop profound ascites consistent with classic “wet form” presentation of FIP before beginning treatment with the 3CLpro inhibitor. To palliate clinical signs in these cats, meloxicam (five oral or subcutaneous doses of 0.3 mg/kg once daily) and subcutaneous fluids were administered daily but discontinued before beginning treatment.
Pulling no punches
Six of the cats showed rapid and complete resolution of clinical signs and have remained healthy for an observation period of eight months after treatment. Two of the cats from the “profound clinical signs” group were euthanized at four and seven days, respectively, after initiating treatment due to severity of their clinical signs. At necropsy, the cat euthanized at four days showed only mild lesions consistent with FIP, and the cat euthanized at seven days showed no lesions consistent with FIP. However, both cats were found to have severe pancreatitis. The authors mention that this was a possible side effect of the meloxicam administration. Viral RNA levels in macrophages from the ascites from all cats were also measured and found to decrease dramatically, commensurate with treatment duration.
This clinical study demonstrated the safety and efficacy of a novel coronavirus inhibitory compound, at least on a small, laboratory scale. While not a clinically applicable treatment yet, this raises the exciting potential of effective treatment for both human and animal coronavirus diseases including FIP, SARS and MERS.
Kim Y, Liu H, Galasiti Kankanamalage AC, et al. Reversal of the progression of fatal coronavirus infection in cats by a broad-spectrum coronavirus protease inhibitor. PLoS Pathog 2016;12(3):e1005531.
Link to article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814111/