title: Mechanism of inhibitory effect of dextran sulfate and heparin on replication of human immunodeficiency virus in vitro.
abstract: The sulfated polysaccharides dextran sulfate and heparin have proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. Dextran sulfate (Mr 5000) and heparin (Mr 15,000) completely protected MT-4 cells against HIV-1-induced cytopathogenicity at a concentration of 25 micrograms/ml. Their 50% inhibitory concentrations were 9.1 micrograms/ml (dextran sulfate) and 7.0 micrograms/ml (heparin), respectively. No toxicity for the host cells was observed with these compounds at a concentration of 625 micrograms/ml. The anti-HIV-1 activity of heparins of various molecular weights correlated well with their anticoagulant activity. On the other hand, with dextran sulfates of low molecular weight (5000, 8000) a significant inhibitory effect on HIV-1 was achieved at a concentration that was not markedly inhibitory to the blood coagulation process. Dextran sulfate and heparin were not inhibitory to HIV-1 reverse transcriptase unless they were used at concentrations in excess of those that inhibited HIV-1 replication. They were highly effective against HIV-1 replication even when present only during the 2-hr virus adsorption period. Studies using radiolabeled HIV-1 virions indicated that dextran sulfate and heparin inhibit virus adsorption to the host cells.
authors: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors: M
authors: M
authors: Baba
authors: R
authors: R
authors: Pauwels
authors: J
authors: J
authors: Balzarini
authors: J
authors: J
authors: Arnout
authors: J
authors: J
authors: Desmyter
authors: E
authors: E
authors: De Clercq
mesh_terms: D000327:Adsorption; D000925:Anticoagulants / Q000494:pharmacology; D016264:Dextran Sulfate; D003911:Dextrans / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects*; D006493:Heparin / Q000097:blood / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000925:Anticoagulants; D003911:Dextrans; D010446:Peptide Fragments; D018894:Reverse Transcriptase Inhibitors; D006493:Heparin; D016264:Dextran Sulfate