Foot-and-mouth disease virus 3C protease (FMDV 3Cpro)

Foot-and-mouth disease virus 3C protease (FMDV 3Cpro) is a chymotrypsin-like cysteine protease that plays a central role in the viral life cycle by processing the viral polyprotein into mature structural and non-structural proteins (UniProt P03305; Sweeney et al., 2007). It is responsible for the majority of proteolytic cleavages required for viral replication and assembly (Grubman & Baxt, 2004). In addition to its role in viral maturation, 3Cpro cleaves essential host cell proteins, including eukaryotic initiation factor 4G (eIF4G) and histone H3, to shut down host translation and transcription, thereby facilitating viral dominance and suppressing the host's innate immune response (Strong & Belsham, 2004). Because of its high conservation across FMDV serotypes and its essentiality for viral survival, 3Cpro is considered a prime target for antiviral drug development (Wang et al., 2011). While no drugs are currently approved for clinical use in livestock, experimental inhibitors such as Rupintrivir and various Michael acceptors have demonstrated potent activity by covalently binding to the active site cysteine (Cys163), effectively halting viral propagation (Sweeney et al., 2007; Wang et al., 2011).

Other names

3C proteasePicornain 3CFMDV 3C3Cpro3C cysteine protease

Inhibition of the 3C cysteine protease activity, which prevents the cleavage of the viral polyprotein into functional units and blocks the suppression of host cell protein synthesis, thereby halting viral replication.