SARS-CoV ORF1b-encoded nonstructural proteins 12-16: replicative enzymes as antiviral targets

Antiviral Res. 2014 Jan:101:122-30. doi: 10.1016/j.antiviral.2013.11.006. Epub 2013 Nov 20.

Abstract

The SARS (severe acute respiratory syndrome) pandemic caused ten years ago by the SARS-coronavirus (SARS-CoV) has stimulated a number of studies on the molecular biology of coronaviruses. This research has provided significant new insight into many mechanisms used by the coronavirus replication-transcription complex (RTC). The RTC directs and coordinates processes in order to replicate and transcribe the coronavirus genome, a single-stranded, positive-sense RNA of outstanding length (∼27-32kilobases). Here, we review the up-to-date knowledge on SARS-CoV replicative enzymes encoded in the ORF1b, i.e., the main RNA-dependent RNA polymerase (nsp12), the helicase/triphosphatase (nsp13), two unusual ribonucleases (nsp14, nsp15) and RNA-cap methyltransferases (nsp14, nsp16). We also review how these enzymes co-operate with other viral co-factors (nsp7, nsp8, and nsp10) to regulate their activity. These last ten years of research on SARS-CoV have considerably contributed to unravel structural and functional details of one of the most fascinating replication/transcription machineries of the RNA virus world. This paper forms part of a series of invited articles in Antiviral Research on "From SARS to MERS: 10years of research on highly pathogenic human coronaviruses".

Keywords: Coronavirus; Nonstructural proteins; Replication; SARS-CoV; Transcription.

Publication types

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

MeSH terms

  • Antiviral Agents / pharmacology*
  • Humans
  • Methyltransferases / antagonists & inhibitors
  • Methyltransferases / metabolism
  • RNA Helicases / antagonists & inhibitors
  • RNA Helicases / metabolism
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors
  • RNA-Dependent RNA Polymerase / metabolism
  • Ribonucleases / antagonists & inhibitors
  • Ribonucleases / metabolism
  • Severe acute respiratory syndrome-related coronavirus / enzymology*
  • Severe acute respiratory syndrome-related coronavirus / physiology*
  • Viral Nonstructural Proteins / antagonists & inhibitors
  • Viral Nonstructural Proteins / metabolism*
  • Virus Replication*

Substances

  • Antiviral Agents
  • Viral Nonstructural Proteins
  • nonstructural protein, coronavirus
  • Methyltransferases
  • RNA-Dependent RNA Polymerase
  • Ribonucleases
  • RNA Helicases