Novel non-HAP class A HBV capsid assembly modulators have distinct in vitro and in vivo profiles

J Virol. 2023 Oct 31;97(10):e0072223. doi: 10.1128/jvi.00722-23. Epub 2023 Sep 27.

Abstract

Chronic hepatitis B is the most important cause of liver cancer worldwide and affects more than 290 million people. Current treatments are mostly suppressive and rarely lead to a cure. Therefore, there is a need for novel and curative drugs that target the host or the causative agent, hepatitis B virus itself. Capsid assembly modulators are an interesting class of antiviral molecules that may one day become part of curative treatment regimens for chronic hepatitis B. Here we explore the characteristics of a particularly interesting subclass of capsid assembly modulators. These so-called non-HAP CAM-As have intriguing properties in cell culture but also clear virus-infected cells from the mouse liver in a gradual and sustained way. We believe they represent a considerable improvement over previously reported molecules and may one day be part of curative treatment combinations for chronic hepatitis B.

Keywords: antiviral therapy; capsid assembly modulator; chronic hepatitis B; hepatitis B virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents* / classification
  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • Capsid Proteins / chemistry
  • Capsid Proteins / drug effects
  • Capsid Proteins / metabolism
  • Capsid* / chemistry
  • Capsid* / drug effects
  • Capsid* / metabolism
  • Cells, Cultured
  • Disease Models, Animal
  • Hepatitis B virus* / chemistry
  • Hepatitis B virus* / drug effects
  • Hepatitis B virus* / growth & development
  • Hepatitis B virus* / metabolism
  • Hepatitis B, Chronic* / drug therapy
  • Hepatitis B, Chronic* / virology
  • Humans
  • In Vitro Techniques
  • Mice
  • Virus Assembly* / drug effects

Substances

  • Antiviral Agents
  • Capsid Proteins