Virtual Screening in Hepatitis B Virus Drug Discovery: Current Stateof- the-Art and Future Perspectives

Curr Med Chem. 2018;25(23):2709-2721. doi: 10.2174/0929867325666180221141451.

Abstract

Hepatitis B Virus (HBV) is a major global health burden. Interferon alpha and nucleos(t)ide analogues are currently the standard-of-care for chronic HBV infection. However, these antiviral agents have limited efficacy and do not result in a sustained virological response in the majority of infected patients. Virtual Screening (VS) strategies have now a strong impact on drug discovery, the strength of this research field has been corroborated by recent contributions in the development of novel drug candidates which are in clinical trials or which are already available in the clinics. In this context, different VS strategies have been applied to HBV in order to discover novel inhibitors. In this review, we summarize the VS efforts to identify and design novel HBV interventions. We believe that the combination of in silico and in vitro tools can lead to faster validation of novel drug targets which could accelerate the HBV drug discovery and development efforts.

Keywords: Hepatitis B Virus; Ligand-based virtual screening; docking; inhibitors; quantitative structure-activity relationships; structure-based virtual screening; workflow..

Publication types

  • Review

MeSH terms

  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Capsid Proteins / antagonists & inhibitors
  • Capsid Proteins / metabolism
  • Hepatitis B / drug therapy*
  • Hepatitis B / pathology
  • Hepatitis B / virology
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / metabolism
  • Humans
  • Molecular Docking Simulation*
  • Organic Anion Transporters, Sodium-Dependent / antagonists & inhibitors
  • Organic Anion Transporters, Sodium-Dependent / metabolism
  • Quantitative Structure-Activity Relationship
  • RNA-Directed DNA Polymerase / chemistry
  • RNA-Directed DNA Polymerase / metabolism
  • Symporters / antagonists & inhibitors
  • Symporters / metabolism
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / metabolism
  • Viral Regulatory and Accessory Proteins

Substances

  • Antiviral Agents
  • Capsid Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Symporters
  • Trans-Activators
  • Viral Regulatory and Accessory Proteins
  • hepatitis B virus X protein
  • sodium-bile acid cotransporter
  • RNA-Directed DNA Polymerase