Sulfonic acid polymers as a new class of human immunodeficiency virus inhibitors.
Four sulfonic acid polymers [poly(4-styrenesulfonic acid)(PSS), poly(anetholesulfonic acid)(PAS), poly(vinylsulfonic acid)(PVS), poly(2-acrylamido-2-methyl-1-propanesulfonic acid)(PAMPS)] have been found to inhibit the cytopathicity of HIV-1 and HIV-2 in MT-4 cells at concentrations that are not toxic to the host cells. The sulfonic acid polymers also inhibited syncytium formation in co-cultures of MOLT-4 cells with HIV-1- or HIV-2-infected HUT-78 cells. They also inhibited binding of anti-gp120 mAb to HIV-1 gp120 and blocked adsorption of HIV-1 virions to MT-4 cells. PSS and PAS, but not PVS and PAMPS, interfered with the binding of OKT4A/Leu3a to the CD4 receptor. The anti-HIV activity of these polyanionic compounds can be ascribed to inhibition of the gp120-CD4 interaction. Sulfonic acid polymers represent a lead of anti-HIV compounds that warrant further evaluation of their therapeutic potential.
Mohan
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Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois, Chicago 60680.
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Baba
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De Clercq
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D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology*; D015704:CD4 Antigens / Q000276:immunology; D002478:Cells, Cultured; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000276:immunology; D006678:HIV / Q000187:drug effects* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism; D015498:HIV-2 / Q000187:drug effects / Q000378:metabolism; D011108:Polymers / Q000138:chemical synthesis / Q000494:pharmacology*; D011145:Polyvinyls / Q000138:chemical synthesis / Q000494:pharmacology*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism; D018894:Reverse Transcriptase Inhibitors; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D015704:CD4 Antigens; D006023:Glycoproteins; D011108:Polymers; D011145:Polyvinyls; D018894:Reverse Transcriptase Inhibitors; D013451:Sulfonic Acids; C008959:lyapolate; C077118:poly(2-acrylamido-2-methyl-1-propanesulfonic acid); C077115:poly(anetholesulfonic acid); D012194:RNA-Directed DNA Polymerase; C077114:styrenesulfonic acid polymer