Cyclic zinc-dithiocarbamate-S,S'-dioxide blocks CXCR4-mediated HIV-1 infection.
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.
Takamune
N
N
Department of Biochemistry, Kumamoto University, Kumamoto, 862-0973, Japan.
Misumi
S
S
Shoji
S
S
D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002459:Cell Fusion / Q000187:drug effects; D002460:Cell Line; D018946:Chemokine CCL5 / Q000494:pharmacology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003499:Cyclic S-Oxides / Q000737:chemistry / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D005434:Flow Cytometry; D015726:Giant Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D009942:Organometallic Compounds / Q000737:chemistry / Q000494:pharmacology*; D011533:Proviruses / Q000187:drug effects / Q000235:genetics; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
C410336:3,6,9,12-tetraazatetradecane-1,14-diylbis(zinc dithiocarbamate)-S,S'-dioxide; D000911:Antibodies, Monoclonal; C515255:CXCL12 protein, human; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003499:Cyclic S-Oxides; D004279:DNA, Viral; D009942:Organometallic Compounds; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D002118:Calcium