Targeting the Achilles heel of the hepatitis B virus: a review of current treatments against covalently closed circular DNA

Drug Discov Today. 2015 May;20(5):548-61. doi: 10.1016/j.drudis.2015.01.008. Epub 2015 Jan 24.

Abstract

Chronic infection with hepatitis B virus (HBV) often leads to the development of liver cancer and cirrhosis, creating immense sociological, clinical and economic burdens worldwide. Although current anti-HBV medications manage to control the disease progression and help restore normal liver functions, they often fail to eliminate the virus completely. A major reason for this failure is the presence of a stable viral genome in the hepatocyte nucleus: the covalently closed circular DNA (cccDNA). Targeting HBV cccDNA is a promising approach that could lead to a complete cure. Here, we review various research approaches that are directed toward eliminating HBV cccDNA. This is a brief, yet comprehensive, summary of current state-of-the-art developments in this emerging area of interest.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / therapeutic use*
  • DNA, Circular / drug effects*
  • DNA, Circular / genetics
  • DNA, Viral / drug effects*
  • DNA, Viral / genetics
  • Drug Design*
  • Genotype
  • Hepatitis B virus / drug effects*
  • Hepatitis B virus / genetics
  • Hepatitis B virus / growth & development
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / virology
  • Humans
  • Molecular Structure
  • Molecular Targeted Therapy
  • Remission Induction
  • Structure-Activity Relationship
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • DNA, Circular
  • DNA, Viral