New hepatitis C virus drug discovery strategies and model systems

Expert Opin Drug Discov. 2012 Sep;7(9):849-59. doi: 10.1517/17460441.2012.711312. Epub 2012 Aug 4.

Abstract

Introduction: Hepatitis C virus (HCV) is a major cause of liver disease worldwide and the leading indication for liver transplantation in the United States. Current treatment options are expensive, not effective in all patients and are associated with serious side effects. Although preclinical, anti-HCV drug screening is still hampered by the lack of readily infectable small animal models, the development of cell culture HCV experimental model systems has driven a promising new wave of HCV antiviral drug discovery.

Areas covered: This review contains a concise overview of current HCV treatment options and limitations with a subsequent in-depth focus on the available experimental models and novel strategies that have, and continue to enable, important advances in HCV drug development.

Expert opinion: With a large cohort of chronically HCV-infected patients progressively developing liver disease that puts them at risk for hepatocellular carcinoma and hepatic decompensation, there is an urgent need to develop effective therapeutics that are well tolerated and effective in all patients and against all HCV genotypes. Significant advances in HCV experimental model development have expedited drug discovery; however, additional progress is needed. Importantly, the current trends and momentum in the field suggests that we will continue to overcome critical experimental challenges to reach this end goal.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • Drug Discovery / methods*
  • Hepacivirus / drug effects*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Models, Biological
  • Replicon / drug effects

Substances

  • Antiviral Agents