Roles of the Picornaviral 3C Proteinase in the Viral Life Cycle and Host Cells

Viruses. 2016 Mar 17;8(3):82. doi: 10.3390/v8030082.


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.

Keywords: 3Cpro; pathogenesis; protease inhibitor; structure; translation initiation; viral replication.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3C Viral Proteases
  • Antiviral Agents / isolation & purification
  • Conserved Sequence
  • Cysteine Endopeptidases / chemistry
  • Cysteine Endopeptidases / genetics
  • Cysteine Endopeptidases / metabolism*
  • Drug Discovery / trends
  • Enzyme Inhibitors / isolation & purification
  • Host-Pathogen Interactions*
  • Humans
  • Picornaviridae / enzymology*
  • Picornaviridae / physiology*
  • Polyproteins / metabolism
  • Protein Binding
  • Protein Processing, Post-Translational
  • RNA, Viral / metabolism
  • Viral Proteins / antagonists & inhibitors
  • Viral Proteins / chemistry
  • Viral Proteins / genetics
  • Viral Proteins / metabolism*
  • Virus Replication


  • Antiviral Agents
  • Enzyme Inhibitors
  • Polyproteins
  • RNA, Viral
  • Viral Proteins
  • Cysteine Endopeptidases
  • 3C Viral Proteases
  • 3C proteases