Virulence determinant of Senecavirus A: 3C protein functions as a protease to cleave viral polyprotein and host...

Senecavirus A (SVA) is an emerging virus, classified into the family Picornaviridae. It causes a severe vesicular disease in pigs. SVA 3C protein, a nonstructural protein, in itself is a protease (3C^pro), harboring the typical chymotrypsin-like fold with an S1 subsite. As a protease, 3C^pro plays a dual role in the replicative cycle of SVA. On the one hand, 3C^pro cleaves the viral polyprotein stepwise to generate different proteins. On the other hand, 3C^pro can specifically degrade a variety of host factors. The degradation of host factors may impair one or even more signaling pathways, making SVA not only efficiently propagate in cells but also ingeniously evade the host's immune responses. Herein, we systematically reviewed SVA 3C^pro involved in its structural characteristics, enzymatic properties, and more importantly its functions in cleaving the viral polyprotein and host proteins, aiming to provide a theoretical insight into the development of SVA-related antivirals.