Targeting Protein-Protein and Protein-Nucleic Acid Interactions for Anti-HIV Therapy

Mattia      Mori; Fabrizio      Manetti; Maurizio      Botta

Abstract

Protein-protein and protein-nucleic acid interactions are involved in many regulatory cellular pathways, playing a key role in cell growth and proliferation, as well as in the progression and development of various diseases such as infectious diseases. Especially in the anti-AIDS research, protein-protein and protein-nucleic acid complexes are being considered as promising targets for pharmaceutical interventions aimed at overcoming the drug resistance observed for most of the classic enzyme inhibitors. Consequently, more and more protein-protein and protein-nucleic acid interaction inhibitors have being identified and developed as candidate agents for antiretroviral therapy. Here, we review the state of the art in the discovery and development of protein-protein and protein-nucleic acid interaction inhibitors that block the main steps of the HIV-1 replication cycle, giving a medicinal chemistry-oriented view of strategies for inhibiting these regulatory interactions that are involved in the entry process, in the dimerization of reverse transcriptase and protease enzymes, and in the activity of the nucleocapsid protein by means of small molecular potential therapeutic agents.

Keywords: AIDS, entry, gp120-CD4, HIV-1, nucleocapsid protein NCp7, reverse transcriptase dimerization, protein-nucleic acid interactions, protein-protein interactions, protease, cytotoxicity