Maturation inhibitors: a new therapeutic class targets the virus structure

AIDS Rev. 2007 Jul-Sep;9(3):162-72.

Abstract

The current standard of care for HIV/AIDS in the developed world is HAART therapy, usually a combination of two reverse transcriptase inhibitors and a protease inhibitor. Despite the success of this regimen, there is a continuing need for new drug options to overcome problems with tolerability and the emergence of viral resistance. In this review we discuss the discovery of a potential new class of antiretroviral therapeutics, known as maturation inhibitors, and the development of the first-in-class compound, bevirimat. Bevirimat is distinguished from the currently available antiretrovirals by its unique target and mode of action. While the specific interactions responsible for activity have yet to be fully characterized, it is clear that the target for bevirimat is the Gag polyprotein precursor, the main structural protein responsible for assembly and budding of virion particles. As basic research continues on the precise mechanism of action of bevirimat, clinical development is progressing, with demonstration of both safety and efficacy in early-stage trials. These encouraging results, coupled with the discovery and development of future generations of maturation inhibitors, suggest that maturation inhibitors may be added to the growing set of tools available to control HIV/AIDS.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / metabolism
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active
  • Clinical Trials as Topic
  • Drugs, Investigational
  • Gene Products, gag / metabolism*
  • HIV / drug effects*
  • HIV / physiology
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • Humans
  • Succinates / chemistry
  • Succinates / metabolism
  • Succinates / pharmacology*
  • Succinates / therapeutic use
  • Triterpenes / chemistry
  • Triterpenes / metabolism
  • Triterpenes / pharmacology*
  • Triterpenes / therapeutic use
  • Virus Assembly / drug effects*

Substances

  • Anti-HIV Agents
  • Drugs, Investigational
  • Gene Products, gag
  • Succinates
  • Triterpenes
  • bevirimat