Coronaviruses infect animals and humans causing a wide range of diseases. The 
diversity of coronaviruses in many mammalian species is contributed by 
relatively high mutation and recombination rates during replication. This 
dynamic nature of coronaviruses may facilitate cross-species transmission and 
shifts in tissue or cell tropism in a host, resulting in substantial change in 
virulence. Feline enteric coronavirus (FECV) causes inapparent or mild enteritis 
in cats, but a highly fatal disease, called feline infectious peritonitis (FIP), 
can arise through mutation of FECV to FIP virus (FIPV). The pathogenesis of FIP 
is intimately associated with immune responses and involves depletion of T 
cells, features shared by some other coronaviruses like Severe Acute Respiratory 
Syndrome Coronavirus. The increasing risks of highly virulent coronavirus 
infections in humans or animals call for effective antiviral drugs, but no such 
measures are yet available. Previously, we have reported the inhibitors that 
target 3C-like protease (3CLpro) with broad-spectrum activity against important 
human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of 
our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal 
once certain clinical and laboratory signs become apparent. We found that 
antiviral treatment led to full recovery of cats when treatment was started at a 
stage of disease that would be otherwise fatal if left untreated. Antiviral 
treatment was associated with a rapid improvement in fever, ascites, lymphopenia 
and gross signs of illness and cats returned to normal health within 20 days or 
less of treatment. Significant reduction in viral titers was also observed in 
cats. These results indicate that continuous virus replication is required for 
progression of immune-mediated inflammatory disease of FIP. These findings may 
provide important insights into devising therapeutic strategies and selection of 
antiviral compounds for further development for important coronaviruses in 
animals and humans.