Multi-targeting the entrance door to block HIV-1.
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.
Borkow
G
G
Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
Lapidot
A
A
D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000378:metabolism; D001483:Base Sequence; D002463:Cell Membrane Permeability / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods*; D015658:HIV Infections / Q000378:metabolism / Q000517:prevention & control* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D015728:Receptors, HIV / Q000037:antagonists & inhibitors / Q000378:metabolism
D019380:Anti-HIV Agents; D015728:Receptors, HIV