New NS5B polymerase inhibitors for hepatitis C

Expert Opin Investig Drugs. 2010 Aug;19(8):963-75. doi: 10.1517/13543784.2010.500285.

Abstract

Importance of the field: The current treatment of chronic hepatitis C based on the combination of pegylated interferon and ribavirin is effective in only 50% of patients. Specific targeted antiviral therapies represent a promising approach to eradicate the infection.

Areas covered in this review: This review focuses on progress towards the development of the hepatitis C virus (HCV) polymerase inhibitors that have entered clinical development in recent years.

What the reader will gain: Nucleos(t)ide analogues target the active site of the HCV polymerase and acts as chain terminators. They have similar activity against all genotypes and the virus has a high genetic barrier to drug resistance. Non-nucleoside inhibitors achieve polymerase inhibition by binding to one of the at least four allosteric enzyme sites. Most of them have a genotype-specific activity and they may select rapidly drug-resistant variants if HCV replication is not completely suppressed. Nonetheless, they provide additional options for addressing the needs of infected patients.

Take home message: NS5B polymerase inhibitors will form an integral part of more effective anti-HCV therapy, in combination with interferon or with other directly acting antiviral agents.

Publication types

  • Review

MeSH terms

  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Therapy, Combination
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Hepacivirus / chemistry
  • Hepacivirus / drug effects*
  • Hepacivirus / enzymology
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Humans
  • Male
  • Nucleosides / pharmacology
  • Nucleosides / therapeutic use
  • Protein Conformation
  • RNA-Dependent RNA Polymerase / antagonists & inhibitors*
  • RNA-Dependent RNA Polymerase / chemistry
  • RNA-Dependent RNA Polymerase / metabolism
  • Structure-Activity Relationship
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Drugs, Investigational
  • Enzyme Inhibitors
  • NS-5 protein, hepatitis C virus
  • Nucleosides
  • Viral Nonstructural Proteins
  • RNA-Dependent RNA Polymerase