Cyclic zinc-dithiocarbamate-S,S'-dioxide blocks CXCR4-mediated HIV-1 infection.

Abstract

To test the anti-human immunodeficiency virus type-1 (HIV-1) activity of 3,6,9,12-tetraazatetradecane-1,14-diylbis(zinc dithiocarbamate)-S,S'-dioxide (cyclic zinc-dithiocarbamate-S, S'-dioxide), MAGI and MAGIC-5 cells were used; the former express CXCR4 and the latter express both CXCR4 and CCR5, which are HIV-1 coreceptors. The compound markedly inhibited HIV-1 X4 (CXCR4-using) viral replication in both MAGI and MAGIC-5 cells. On the other hand, the replication of HIV-1 R5X4 (both CXCR4-and CCR5-using) in MAGI cells but not MAGIC-5 cells was inhibited by the compound. The compound was found to specifically inhibit HIV-1 (X4) envelope-mediated cell-to-cell fusion, binding of anti-CXCR4 monoclonal antibody (12G5) to CXCR4 expressed on the surface of cells, and calcium flux induced by stromal-derived factor-1alpha (SDF-1alpha) bound to CXCR4. The results suggest that the compound inhibited CXCR4-mediated HIV-1 infection by influencing to the HIV-1 coreceptor activity of CXCR4.

• Authors: N Takamune, S Misumi, S Shoji
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 272 Issue 2 Pg. 351-6 (Jun 07 2000) ISSN: 0006-291X [Print] United States
• PMID: 10833417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Academic Press.

Chemical References

• 3,6,9,12-tetraazatetradecane-1,14-diylbis(zinc dithiocarbamate)-S,S'-dioxide
• Antibodies, Monoclonal
• CXCL12 protein, human
• Chemokine CCL5
• Chemokine CXCL12
• Chemokines, CXC
• Cyclic S-Oxides
• DNA, Viral
• Organometallic Compounds
• Receptors, CCR5
• Receptors, CXCR4
• Calcium

Topics

• Antibodies, Monoclonal (immunology, pharmacology)
• Calcium (metabolism)
• Cell Fusion (drug effects)
• Cell Line
• Chemokine CCL5 (pharmacology)
• Chemokine CXCL12
• Chemokines, CXC (antagonists & inhibitors, pharmacology)
• Cyclic S-Oxides (chemistry, pharmacology)
• Cytopathogenic Effect, Viral (drug effects)
• DNA, Viral (analysis, genetics)
• Flow Cytometry
• Giant Cells (drug effects, metabolism, pathology, virology)
• HIV-1 (drug effects, genetics, metabolism, physiology)
• Humans
• Inhibitory Concentration 50
• Organometallic Compounds (chemistry, pharmacology)
• Proviruses (drug effects, genetics)
• Receptors, CCR5 (genetics, immunology, metabolism)
• Receptors, CXCR4 (antagonists & inhibitors, genetics, immunology, metabolism)