Computer-aided design and discovery of protein–protein interaction inhibitors as agents for anti-HIV therapy

Abstract

Protein–protein interactions (PPI) are involved in most of the essential processes that occur in organisms. In recent years, PPI have become the object of increasing attention in drug discovery, particularly for anti-HIV drugs. Although the use of combinations of existing drugs, termed highly active antiretroviral therapy (HAART), has revolutionized the treatment of HIV/AIDS, problems with these agents, such as the rapid emergence of drug-resistant HIV-1 mutants and serious adverse effects, have highlighted the need for further discovery of new drugs and new targets. Numerous investigations have shown that PPI play a key role in the virus’s life cycle and that blocking or modulating them has a significant therapeutic potential. Here we summarize the recent progress in computer-aided design of PPI inhibitors, mainly focusing on the selection of the drug targets (HIV enzymes and virus entry machinery) and the utilization of peptides and small molecules to prevent a variety of protein–protein interactions (viral–viral or viral–host) that play a vital role in the progression of HIV infection.

Keywords:

• HIV-1
• protein-protein interactions
• inhibitors
• computer-aided design & discovery
• drug target

Acknowledgements

This paper was presented at the 7th CMTPI conference in Seoul, 8–12 October 2013. This work was supported by Russian Foundation of Basic Research [grant number 13-04-91455_NIH-a].