Blocking the docking of HIV-1
- Department of Immunology and Molecular Pathology, University College London, 46 Cleveland Street, London W1T 4JF, United Kingdom
There are estimated to be >42 million people worldwide who live with HIV-1 infection. Any novel means of treating infection therefore will be greeted with great interest. The current generation of antiretroviral drugs inhibits the viral enzymes, reverse transcriptase and protease (1), and where available has resulted in a 65% reduction of AIDS mortality. Nevertheless, new drugs will be needed as drug resistance emerges, and all steps in the replication of HIV-1 are fair game as potential drug targets (Fig. 1).
Simplified replication cycle of HIV-1. Several of the steps that can be blocked by actual or potential drugs are numbered: 1, docking to CD4, the topic of this commentary; 2, interaction with the chemokine coreceptor; 3, inhibiting fusion of the viral envelope with the cell membrane; 4, reverse transcriptase inhibitors; 5, integrase inhibitors; 6, prevention of viral transcription such as Tat antagonists; and 7, protease inhibitors. Attacking the virus with several drugs in combination has been the key to successful clinical therapy thus far.
In this issue of PNAS, Pin-Fang Lin and colleagues at Bristol-Myers Squibb (2) describe a small molecular weight inhibitor of HIV-1 infection that acts by blocking the very first step in the infection process, namely, the binding of the viral envelope glycoprotein (gp120) to its cell surface receptor, CD4. …
