title: Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells.
abstract: The Picornaviridae family comprises a large group of non-enveloped viruses that have a major impact on human and veterinary health. The viral genome contains one open reading frame encoding a single polyprotein that can be processed by viral proteinases. The crucial 3C proteinases (3C(pro)s) of picornaviruses share similar spatial structures and it is becoming apparent that 3C(pro) plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3C(pro) are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3C(pro) can induce the cleavage of certain cellular factors required for transcription, translation and nucleocytoplasmic trafficking to modulate cell physiology for viral replication. Due to interactions between 3C(pro) and these essential factors, 3C(pro) is also involved in viral pathogenesis to support efficient infection. Furthermore, based on the structural conservation, the development of irreversible inhibitors and discovery of non-covalent inhibitors for 3C(pro) are ongoing and a better understanding of the roles played by 3C(pro) may provide insights into the development of potential antiviral treatments. In this review, the current knowledge regarding the structural features, multiple functions in the viral life cycle, pathogen host interaction, and development of antiviral compounds for 3C(pro) is summarized.
authors.affiliation: Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. sundi0921@126.com.|Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. sundi0921@126.com.
authors.forename: Di
authors.initials: D
authors.lastname: Sun
authors.affiliation: Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. sophia_cs@163.com.|Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. sophia_cs@163.com.|Key Laboratory of Animal Disease and Human Health of Sichuan Province, Wenjiang, Chengdu 611130, China. sophia_cs@163.com.
authors.forename: Shun
authors.initials: S
authors.lastname: Chen
authors.affiliation: Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. chenganchun@vip.163.com.|Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. chenganchun@vip.163.com.|Key Laboratory of Animal Disease and Human Health of Sichuan Province, Wenjiang, Chengdu 611130, China. chenganchun@vip.163.com.
authors.forename: Anchun
authors.initials: A
authors.lastname: Cheng
authors.affiliation: Avian Disease Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. mshwang@163.com.|Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Wenjiang, Chengdu 611130, China. mshwang@163.com.|Key Laboratory of Animal Disease and Human Health of Sichuan Province, Wenjiang, Chengdu 611130, China. mshwang@163.com.
authors.forename: Mingshu
authors.initials: M
authors.lastname: Wang
mesh_terms: D000086042:3C Viral Proteases; D000998:Antiviral Agents / Q000302:isolation & purification; D017124:Conserved Sequence; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055808:Drug Discovery / Q000639:trends; D004791:Enzyme Inhibitors / Q000302:isolation & purification; D054884:Host-Pathogen Interactions; D006801:Humans; D010849:Picornaviridae / Q000201:enzymology* / Q000502:physiology*; D020815:Polyproteins / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D012367:RNA, Viral / Q000378:metabolism; D014764:Viral Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D020815:Polyproteins; D012367:RNA, Viral; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases
keywords: 3Cpro; pathogenesis; protease inhibitor; structure; translation initiation; viral replication