Feline infectious peritonitis virus 3C-like protease (3CLpro)

The Feline infectious peritonitis virus 3C-like protease (3CLpro), also known as the main protease (Mpro) or NSP5, is a critical cysteine protease required for the maturation of the feline coronavirus (FCoV), the causative agent of Feline Infectious Peritonitis (FIP) (Kim et al., 2016, PLOS Pathogens). This enzyme is responsible for the proteolytic processing of the large viral polyproteins, pp1a and pp1ab, at multiple conserved sites to release functional non-structural proteins essential for viral replication and transcription (Pedersen et al., 2018, Journal of Feline Medicine and Surgery). Because 3CLpro possesses a unique substrate specificity that is not found in host cell proteases, it serves as a highly selective and effective target for antiviral therapy (UniProt P0C6V2). Small molecule inhibitors like GC376 bind to the catalytic cysteine residue of the enzyme, effectively blocking its activity and leading to significant clinical recovery in cats with both effusive and non-effusive FIP (Kim et al., 2016). Recent studies have also demonstrated that 3CLpro inhibitors developed for human coronaviruses, such as Nirmatrelvir, show potent cross-species activity against the FIPV enzyme, facilitating new avenues for veterinary treatment (Cook et al., 2022, Viruses).

Other names

Main proteaseMproNSP53C-like cysteine proteaseFIPV 3CLproC30 endopeptidase

Inhibition of the 3C-like protease prevents the proteolytic cleavage of the viral polyproteins pp1a and pp1ab into functional non-structural proteins, thereby halting the assembly of the viral replication-transcription complex and stopping viral replication.