Human immunodeficiency virus-1 gp120 V3 loop for anti-acquired immune deficiency syndrome drug discovery: computer-aided approaches to the problem solving

Abstract

Introduction: 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.Areas covered: 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.Expert opinion: 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.