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Published online before print August 1, 2003
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0403177

Received for publication April 24, 2003.
Revised June 19, 2003.
Accepted for publication July 2, 2003.

Article

Specific CD4 down-modulating compounds with potent anti-HIV activity

Kurt Vermeire and Dominique Schols @

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium

@ To whom correspondence should be addressed. E-mail: dominique.schols{at}rega.kuleuven.ac.be.


  Abstract

Despite the availability of the current clinically approved anti-HIV drugs, new classes of effective antiviral agents are still urgently needed to combat AIDS. A promising approach for drug development and vaccine design involves targeting research on HIV-1 entry, a multistep process that comprises viral attachment, coreceptor interactions, and fusion. Determination of the viral entry process in detail has enabled the design of specific agents that can inhibit each step in the HIV entry process. Therapeutic agents that interfere with the binding of the HIV envelope glycoprotein gp120 to the CD4 receptor (e.g., PRO 542, PRO 2000, and CV-N) or the coreceptors CCR5 and CXCR4 (e.g., SCH-C and AMD3100) are briefly outlined in this review. The anti-HIV activity of cyclotriazadisulfonamides, a novel class of compounds with a unique mode of action by down-modulating the CD4 receptor in lymphocytic and monocytic cells, is especially highlighted. On the basis of the successful results of T-20, the first approved entry inhibitor, the development of effective antiretrovirals that block HIV entry will certainly be further encouraged.

Key Words: HIV entry inhibitors • CD4 receptor down-modulation • CADA CCR5 • CXCR4 antagonists




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