An Intracellular Model of Hepatitis B Viral Infection: An In Silico Platform for Comparing Therapeutic Strategies

Viruses. 2020 Dec 23;13(1):11. doi: 10.3390/v13010011.

Abstract

Hepatitis B virus (HBV) is a major focus of antiviral research worldwide. The International Coalition to Eliminate HBV, together with the World Health Organisation (WHO), have prioritised the search for a cure, with the goal of eliminating deaths from viral hepatitis by 2030. We present here a comprehensive model of intracellular HBV infection dynamics that includes all molecular processes currently targeted by drugs and agrees well with the observed outcomes of several clinical studies. The model reveals previously unsuspected kinetic behaviour in the formation of sub-viral particles, which could lead to a better understanding of the immune responses to infection. It also enables rapid comparative assessment of the impact of different treatment options and their potential synergies as combination therapies. A comparison of available and currently developed treatment options reveals that combinations of multiple capsid assembly inhibitors perform best.

Keywords: antiviral therapy; hepatitis B virus; intracellular model; packaging signal; virus assembly.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Computer Simulation
  • Hepatitis B / drug therapy
  • Hepatitis B / virology*
  • Hepatitis B virus / drug effects
  • Hepatitis B virus / physiology*
  • Hepatitis B, Chronic / drug therapy
  • Hepatitis B, Chronic / virology
  • Humans
  • Kinetics
  • Models, Biological
  • Virus Assembly / drug effects
  • Virus Internalization / drug effects
  • Virus Replication / drug effects

Substances

  • Antiviral Agents