Peptides as new inhibitors of HIV-1 reverse transcriptase and integrase

Curr Med Chem. 2003 Sep;10(18):1765-78. doi: 10.2174/0929867033457007.


Current treatments of human immunodeficiency virus type 1 (HIV-1) infection consist in the combination of drugs targeting reverse transcriptase (RT) and protease (PR). Despite the multiple clinical benefits of this combination therapy, the emergence of resistance highlights the need for new anti-HIV agents. Agents able to interfere with additional steps of viral replication, such as integration of viral DNA in the host genome, would improve the antiviral potency of the treatment. In this regard, we have focused our interest on peptide-based compounds that have been shown to exhibit potential inhibition of RT and integrase (IN) activities in vitro and in vivo. Recently, the expansion of powerful technologies which allow the selection of peptides exhibiting high affinity for a target protein have provided a new approach to selecting potential anti-HIV drugs. Furthermore, efforts to characterize the protein-protein interactions involved in efficient reverse transcription and integration, as well as the determination of the enzyme structure, have generated a very useful source of data for the development of peptide inhibitors. Finally, while this class of compounds has long been considered as poor drug candidates, current knowledge on improving the stability and bioavailability of these agents would lead to the effective use of peptides in therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Anti-HIV Agents / therapeutic use
  • Drug Design
  • HIV Infections / drug therapy
  • HIV Infections / virology
  • HIV Integrase Inhibitors / chemistry
  • HIV Integrase Inhibitors / pharmacology*
  • HIV Integrase Inhibitors / therapeutic use
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • Humans
  • Models, Biological
  • Peptide Library
  • Peptides / chemistry
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Reverse Transcriptase Inhibitors / therapeutic use


  • Anti-HIV Agents
  • HIV Integrase Inhibitors
  • Peptide Library
  • Peptides
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase