Comparative Evaluation of GS-441524, Teriflunomide, Ruxolitinib, Molnupiravir, Ritonavir, and Nirmatrelvir for In Vitro Antiviral Activity against Feline Infectious Peritonitis Virus

Feline infectious peritonitis (FIP), caused by feline coronavirus (FcoV), is considered one of the most enigmatic diseases in cats. Developing effective drugs for FIP is crucial due to its global prevalence and severity. In this study, six antiviral drugs were tested for their cytotoxicity, cell viability, and antiviral efficacies in Crandell-Reese feline kidney cells. A cytotoxicity assay demonstrated that these drugs were safe to be used with essentially no cytotoxicity with concentrations as high as 250 mu Mfor ruxolitinib; 125 mu Mfor GS441524; 63 mu Mfor teriflunomide, molnupiravir, and nirmatrelvir; and 16 mu M for ritonavir. GS441524 and nirmatrelvir exhibited the least detrimental effects on the CRFK cells, with 50% cytotoxic concentration (CC50) values of 260.0 mu M and 279.1 mu M, respectively, while ritonavir showed high toxicity (CC50 = 39.9 mu M). In the dose-response analysis, GS441524, nirmatrelvir, and molnupiravir demonstrated promising results with selectivity index values of 165.54, 113.67, and 29.27, respectively, against FIPV. Our study suggests that nirmatrelvir and molnupiravir hold potential for FIPV treatment and could serve as alternatives to GS441524. Continued research and development of antiviral drugs are essential to ensure the well-being of companion animals and improve our preparedness for future outbreaks of coronaviruses affecting animals and humans alike.

Automated summary

Feline infectious peritonitis (FIP) is an enigmatic disease in cats, and this study tested six antiviral drugs for their efficacy against FIPV. Nirmatrelvir and molnupiravir showed potential as alternatives to GS441524 for FIPV treatment. Continued research and development of antiviral drugs are crucial for the well-being of companion animals and preparedness for future outbreaks.