Human immunodeficiency virus-1 gp120 V3 loop for anti-acquired immune deficiency syndrome drug discovery: computer-aided approaches to the problem solving.
BACKGROUND
The V3 loop on gp120 from HIV-1 is a focus of many research groups involved in anti-AIDS drug development because this region of the protein is the principal target for neutralizing antibodies and determines the preference of the virus for T-lymphocytes or primary macrophages.


METHODS
This review summarizes findings related to the 3D structure, conformational mobility, function, antigenicity and immunogenicity of the HIV-1 V3 loop. Particular consideration is given to the V3 loop core sequence Gly-Pro-Gly-Arg/Gln-Ala-Phe, which forms the HIV-1 gp120 immunogenic tip, the role of which has not been completely determined in the virus pathogenesis. New computer-aided approaches for designing potential HIV-1 entry inhibitors are illustrated by a series of examples in which promising basic structures for the V3-based anti-AIDS drug researches have been constructed. Special focus is given to recent studies aimed at defining the structurally conservative V3 sites that may present the HIV-1 weak points most suitable for therapeutic intervention. Finally, the article also discusses how this information can be used to develop novel, potent and broad anti-AIDS agents.


CONCLUSIONS
Data on the structure and function of the HIV-1 V3 loop prove convincingly that, in spite of disappointing progress > 20 years, this mysterious site of gp120 (comprising at least three structural motifs recurring in various viral isolates) still remains one of the most attractive targets for the anti-AIDS drug development.
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Kuprevich Street 5/2, 220141 Minsk, Republic of Belarus  +375 17 2678263 ;  +375 17 2241214 ;  andrianov@iboch.bas-net.by.
Alexander M
AM
Andrianov