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 (3Cpros) of picornaviruses share similar spatial structures and it is becoming apparent that 3Cpro plays a significant role in the viral life cycle and virus host interaction. Importantly, the proteinase and RNA-binding activity of 3Cpro are involved in viral polyprotein processing and the initiation of viral RNA synthesis. In addition, 3Cpro 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 3Cpro and these essential factors, 3Cpro 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 3Cpro are ongoing and a better understanding of the roles played by 3Cpro 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 3Cpro is summarized.
Highlights
Members of the Picornaviridae family are positive-strand viruses that have a major impact on the health of humans and animals
RNA-binding activity of 3C proteinases (3Cpros) is important for initiating viral RNA synthesis. 3C proteinases (3Cpro s)and its 3ABC, 3BC, 3BCD and P3 precursors can stimulate RNA synthesis at different levels
The translation and replication of the picornaviral genome utilize the host translation machinery and the alteration and cleavage of host proteins lead to inhibition of host translation and transcription and nucleus-cytoplasm transport. 3Cpro and the 3CD precursor are involved in many steps of gene expression to hijack cellular resources and to generate an optimal intracellular environment for the virus life cycle
Summary
Members of the Picornaviridae family are positive-strand viruses that have a major impact on the health of humans and animals This family is composed of 29 genera, including Aphthovirus, Cardiovirus, Kunsagivirus, Enterovirus, Hepatovirus and Sicinivirus [1,2,3]. Picornaviruses are small, non-enveloped viruses containing a single-stranded RNA genome with a length of 7.0–8.5 kb. The viral genome contains one open reading frame that encodes a single polyprotein comprising a structural protein P1 region and non-structural protein P2 and P3 regions. RNA is linked to a small viral-encoded protein (VPg), instead of 7-methylguanosine, which is necessary. In. In addition, addition, we we compare compare the pro in functions of 3Cpro the pathogenesis process of different picornaviruses. 5′NTR consists a cloverleaf viral-encoded protein, 3B (VPg), is to linked the 51 terminus of the
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