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

• Published in: SAR and QSAR in environmental research Vol. 25; no. 6; pp. 457 - 471
• Main Authors: Veselovsky, A.V., Zharkova, M.S., Poroikov, V.V., Nicklaus, M.C.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.01.2014
• Subjects: Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Computer-Aided Design; computer-aided design & discovery; Drug Design; drug target; HIV Infections - drug therapy; HIV-1; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; inhibitors; Protein Interaction Mapping; protein-protein interactions; Quantitative Structure-Activity Relationship; HIV-1; inhibitors; computer-aided design & discovery; drug target; protein-protein interactions
• ISSN: 1062-936X; 1029-046X
• DOI: 10.1080/1062936X.2014.898689

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.