Current drug discovery strategies for treatment of hepatitis C virus infection

J Pharm Pharmacol. 2011 Jul;63(7):883-92. doi: 10.1111/j.2042-7158.2011.01267.x. Epub 2011 May 19.

Abstract

Objectives: Hepatitis C virus (HCV) infection represents a major worldwide-health problem. The current standard of care is combination therapy with pegylated interferon and ribavirin, which achieves a successful response in only approximately 40% of genotype I patients.

Key findings: The biology of HCV infection has been under intensive research and important progress has been made in understanding the replication cycle of the virus. Several therapeutic targets have been under investigation, such as NS3 protease, NS4A replicase and NS5B polymerase. New potential targets, such as NS2 protease, as well as CD-81 and claudin-1 entry co-receptors, have also been identified.

Summary: Clinical evaluations of drug candidates targeting NS3 protease, NS4A cofactor, and NS5B polymerase have demonstrated the potential of developing small molecules that interfere with the replication of the virus. Additional issues, including genotype coverage, resistant mutations, and combination therapy represent major challenges for future drug discovery efforts.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / pharmacology*
  • Biological Availability
  • Carrier Proteins / antagonists & inhibitors
  • Drug Design
  • Drug Discovery*
  • Half-Life
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / physiology
  • Hepatitis C / drug therapy*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Serine Proteinase Inhibitors / adverse effects
  • Serine Proteinase Inhibitors / pharmacokinetics
  • Serine Proteinase Inhibitors / pharmacology
  • Viral Nonstructural Proteins / antagonists & inhibitors

Substances

  • Antiviral Agents
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • NS3 protein, hepatitis C virus
  • NS4A cofactor peptide, Hepatitis C virus
  • Serine Proteinase Inhibitors
  • Viral Nonstructural Proteins
  • NS-5 protein, hepatitis C virus