Multi-targeting the Entrance Door to Block HIV-1

Authors: G. Borkow; A. Lapidot

Source: Current Drug Targets - Infectious Disorders, Volume 5, Number 1, March 2005 , pp. 3-15(13)

Publisher: Bentham Science Publishers

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Abstract:

The multistep nature of HIV-1 entry provides multisite targeting at the entrance door of HIV-1 to cells. Blocking HIV-1 entry to its host cells has clear advantages over blocking subsequent stages in the life cycle of the virus. Indeed, potent cooperative and synergistic inhibition of HIV-1 proliferation has been observed in in vitro studies with several entry inhibitor combinations, interacting with different steps of the HIV-1-cell entry cascade. Targeting a compound to several steps of the viral-cell entry and also to subsequent steps in the viral life cycle promises an even more effective therapeutic, by reducing the probability of HIV-1 to develop resistance. Using one drug that can target multiple sites and / or steps in the viral life cycle will have obvious advantages in clinical use. In this article we review the multistep process of HIV-1 cell entry and the current repertoire of inhibitors of this critical stage in the viral life cycle, and introduce an example of multisite HIV-1 targeting of the cell entry and subsequent critical steps in the viral life cycle.

Keywords: hiv-1; entry inhibitors; gp120; gp41; membrane fusion; ccr5; cxcr4; aacs

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568005053174645

Affiliations: 1: Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100 Israel.

Publication date: 2005-03-01