Pentosan polysulfate, a sulfated oligosaccharide, is a potent and selective anti-HIV agent in vitro.
Several sulfated oligo- or polysaccharides such as pentosan polysulfate, fucoidan, dextran sulfate, heparin and iota-, kappa- and lambda-carrageenans proved to be potent and selective inhibitors of human immunodeficiency virus type 1 (HIV-1) in vitro. The most potent anti-HIV-1 activity was recorded for the oligosaccharide pentosan polysulfate, its 50% antiviral effective dose (ED50) being 0.19 microgram/ml in MT-4 cells. It inhibited HIV-1 antigen expression in HUT-78 cells at an ED50 of 0.02 microgram/ml, and complete inhibition of HIV-1 antigen expression was obtained at a concentration of 4.0 micrograms/ml. No toxicity for MT-4 cells was observed with pentosan polysulfate at a concentration of 2500 micrograms/ml. The anticoagulant activity of pentosan polysulfate was more than ten-fold lower than that of heparin (14.4 and 177 U/mg, respectively). In fact, pentosan polysulfate achieved its anti-HIV-1 activity at a concentration that is 370-fold below its anticoagulant threshold (1 U). Pentosan polysulfate inhibits virus adsorption to the cells, as was demonstrated by monitoring the association of radiolabeled HIV-1 virions with MT-4 cells.
Baba
M
M
Department of Human Biology, Rega Institute for Medical Research, University of Leuven, Belgium.
Nakajima
M
M
Schols
D
D
Pauwels
R
R
Balzarini
J
J
De Clercq
E
E
D000327:Adsorption; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology; D000998:Antiviral Agents; D001777:Blood Coagulation / Q000187:drug effects; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D010426:Pentosan Sulfuric Polyester / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D011134:Polysaccharides / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors
D000925:Anticoagulants; D000998:Antiviral Agents; D011134:Polysaccharides; D018894:Reverse Transcriptase Inhibitors; D010426:Pentosan Sulfuric Polyester; C007789:fucoidan