Polymerases of hepatitis C viruses and flaviviruses

Structural and mechanistic insights and drug development

Célia Caillet-Saguy, Siew Pheng Lim, Pei-Yong Shi, Julien Lescar, Stéphane Bressanelli

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

The family Flaviviridae comprises several major human pathogens including hepatitis C virus (genus hepacivirus), yellow fever virus, West Nile virus and dengue virus (genus flavivirus). Flaviviridae genomes comprise a single-stranded RNA segment encoding a single polyprotein that is subsequently processed into 10 mature viral proteins. The nonstructural proteins are released from the C-terminus of the polyprotein and contribute to the infectious cycle by forming membrane-bound, multi-protein compartments within host cells, named the replication complexes, where synthesis of new viral genomes takes place. Two nonstructural proteins are endowed with multiple enzymatic activities and represent important targets against which specific antiviral inhibitors have been developed. X-ray crystal structures of these viral enzymes as well as in-depth understanding of the molecular basis of their activities have contributed tremendously to the development of antiviral compounds, currently approved or in advanced clinical trials for hepatitis C treatment. One of the prime targets is the RNA-dependent RNA polymerase (RdRp, NS5B for hepatitis C virus, NS5 for flaviviruses). Here we review current knowledge of the structural basis for viral RNA synthesis by NS5B and NS5. These data offer perspectives for further drug design and constitute major advances in our basic understanding of viral RdRp. They thus point to future research directions in the field.

Original languageEnglish (US)
Pages (from-to)8-16
Number of pages9
JournalAntiviral Research
Volume105
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

Fingerprint

Flavivirus
Flaviviridae
Hepacivirus
Polyproteins
Antiviral Agents
Yellow fever virus
Pharmaceutical Preparations
RNA Replicase
West Nile virus
Viral Structures
Dengue Virus
Viral Genome
Drug Design
Viral RNA
Viral Proteins
Hepatitis C
Protein C
Proteins
X-Rays
Clinical Trials

Keywords

  • Flaviviridae
  • Non-nucleoside inhibitors
  • Nucleoside inhibitors
  • RdRp regulation
  • RNA synthesis
  • RNA-dependent RNA polymerase

ASJC Scopus subject areas

  • Virology
  • Pharmacology
  • Medicine(all)

Cite this

Polymerases of hepatitis C viruses and flaviviruses : Structural and mechanistic insights and drug development. / Caillet-Saguy, Célia; Lim, Siew Pheng; Shi, Pei-Yong; Lescar, Julien; Bressanelli, Stéphane.

In: Antiviral Research, Vol. 105, No. 1, 2014, p. 8-16.

Research output: Contribution to journalArticle

Caillet-Saguy, Célia ; Lim, Siew Pheng ; Shi, Pei-Yong ; Lescar, Julien ; Bressanelli, Stéphane. / Polymerases of hepatitis C viruses and flaviviruses : Structural and mechanistic insights and drug development. In: Antiviral Research. 2014 ; Vol. 105, No. 1. pp. 8-16.
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