Therapeutic potential of peptide motifs against HIV-1 reverse transcriptase and integrase

Multiple clinical benefits have been obtained thanks to the combination of drugs targeting several steps of the HIV-1 replication. However, despite such combination therapy, complete eradication of the virus cannot be attained. Moreover, emergence of resistance observed under treatment and the lengthening life expectancy of treated patients highlight the need for new anti-HIV agents. Peptide-based compounds that exhibit anti RT and anti integrase activities were particularly described. Active peptides have been obtained from several ongoing approaches. The study of interaction between viral proteins inside the preintegration complex, and the growing knowledge of interactions between viral proteins and cellular partners, have generated a useful source of data for the development of peptide inhibitors. Recent data were also obtained from the observation that viral enzymes such as RT and integrase are fully active when they are in a dimeric (RT) or oligomeric state. Peptides derived from the interface of dimers are also of interest. The obtention of efficient small molecules as competitive oligomerization inhibitors is problematic, but anyway, improved cellular uptake and chemical modifications that were obtained in the past ten years allowed numerous peptide drugs to reach the clinic. Finally, a new promising class of peptide inhibitors is emerging called "shiftides", which interfere with the ability of IN to adopt an oligomeric active state.