title: SARS-CoV ORF1b-encoded nonstructural proteins 12-16: replicative enzymes as antiviral targets.
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".
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257 - CNRS et Aix-Marseille Université, ESIL Case 925, 13288 Marseille, France.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Subissi
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257 - CNRS et Aix-Marseille Université, ESIL Case 925, 13288 Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Imbert
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257 - CNRS et Aix-Marseille Université, ESIL Case 925, 13288 Marseille, France.
authors.forename: François
authors.initials: F
authors.lastname: Ferron
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257 - CNRS et Aix-Marseille Université, ESIL Case 925, 13288 Marseille, France.
authors.forename: Axelle
authors.initials: A
authors.lastname: Collet
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257 - CNRS et Aix-Marseille Université, ESIL Case 925, 13288 Marseille, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Coutard
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257 - CNRS et Aix-Marseille Université, ESIL Case 925, 13288 Marseille, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Decroly
authors.affiliation: Laboratoire Architecture et Fonction des Macromolécules Biologiques (AFMB), UMR 7257 - CNRS et Aix-Marseille Université, ESIL Case 925, 13288 Marseille, France. Electronic address: bruno.canard@afmb.univ-mrs.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Canard
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020365:RNA Helicases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors / Q000378:metabolism; D012260:Ribonucleases / Q000037:antagonists & inhibitors / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology* / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D000998:Antiviral Agents; D017361:Viral Nonstructural Proteins; C087633:nonstructural protein, coronavirus; D008780:Methyltransferases; D012324:RNA-Dependent RNA Polymerase; D012260:Ribonucleases; D020365:RNA Helicases
keywords: Coronavirus; Nonstructural proteins; Replication; SARS-CoV; Transcription