NS5A inhibitors in the treatment of hepatitis C

J Hepatol. 2013 Aug;59(2):375-82. doi: 10.1016/j.jhep.2013.03.030. Epub 2013 Apr 6.

Abstract

Hepatitis C virus infection is a major health problem worldwide and no vaccine has yet been developed against this virus. In addition, currently approved pharmacotherapies achieve suboptimal cure rates and have side effects that result in non-compliance and premature treatment discontinuation. Significant research has been devoted to developing direct-acting antiviral agents that inhibit key viral functions. In particular, several novel drug candidates that inhibit the viral non-structural protein 5A (NS5A) have been demonstrated to possess high potency, pan-genotypic activity, and a high barrier to resistance. Clinical trials using combination therapies containing NS5A inhibitors have reported results that promise high cure rates and raise the possibility of developing interferon-free, all-oral regimens.

Keywords: DAA; Daclatasvir; HCV; Hepatitis C virus; IFN; IRES; NS; NS5A inhibitor; RNA-dependent RNA polymerase; RVR; RdRp; Resistance; SVR; UTR; cEVR; complete early virologic response; direct acting antiviral; hepatitis C virus; interferon; internal ribosome entry site; nonstructural; rapid virologic response; sustained virological response; untranslated region.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Anilides / therapeutic use
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use
  • Carbamates / therapeutic use
  • Clinical Trials as Topic
  • Drug Resistance, Viral / genetics
  • Drug Therapy, Combination
  • Fluorenes / therapeutic use
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Imidazoles / therapeutic use
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / genetics
  • Viral Nonstructural Proteins / physiology

Substances

  • Anilides
  • Antiviral Agents
  • Benzimidazoles
  • Carbamates
  • Fluorenes
  • Imidazoles
  • NS-5 protein, hepatitis C virus
  • Viral Nonstructural Proteins
  • ledipasvir
  • ombitasvir
  • daclatasvir