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An Insight on the Leading HIV Entry Inhibitors

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The main strategies nowadays to fight AIDS rely on chemical therapy to inhibit the reverse transcriptase or protease of HIV. However, a synthetic 36 amino-acids peptide that blocks the entry of the virus in the target cells (enfuvirtide) has recently reached approval for clinical application. This molecule may probably be just the leader of a new generation of drugs that is about to emerge to interrupt the first step in the HIV life cycle, i.e. preventing the virus from actually entering cells. This paper reviews the enfuvirtide path from clinical trials to the attempts to detail its molecular-level mode of action. It is commonly accepted that this peptide would block the fusion between viral and cell plasma membrane through binding to the N-terminal heptad repeat (NHR) region of the viral protein gp41. However, there has been growing evidence that this model of action may be unrealistic, the action of enfuvirtide being more complex and diverse than initially thought. Membrane-assisted local concentration increase and interference with gp120/co-receptor docking may also contribute for the inhibitory action of the peptide. Selected HIV-entry inhibitors on clinical trials are presented to characterize the future drugs in the market in this class.

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Keywords: AIDS; Entry; HIV; attachment; binding; chemokine; clinical trial; co-receptor; enfuvirtide; entrance inhibitor; fusion; peptide; receptor; synergism; virus

Document Type: Research Article

Affiliations: Centro de Quimica e Bioquimica, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande C8, 1749-016 Lisboa, Portugal;

Publication date: January 1, 2006

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  • Recent Patents on Anti-Infective Drug Discovery publishes review articles on recent patents in the field of anti-infective drug discovery e.g. on novel bioactive compounds, analogs & targets. A selection of important and recent patents on anti-infective drug discovery is also included in the journal. The journal is essential reading for all researchers involved in anti-infective drug design and discovery.
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