Document 0711
 DOCN  M9650711
 TI    Low anticoagulant heparin retains anti-HIV type 1 activity in vitro.
 DT    9605
 AU    Coombe DR; Harrop HA; Watton J; Mulloy B; Barrowcliffe TW; Rider CC;
       Institute for Child Health Research, Perth, Western Australia.
 SO    AIDS Res Hum Retroviruses. 1995 Nov;11(11):1393-6. Unique Identifier :
       AIDSLINE MED/96159137
 AB    Heparin is a potent inhibitor of HIV-1 replication, in addition to being
       a well-established inhibitor of blood coagulation. The major
       anticoagulant activity of heparin results from binding to the plasma
       protein antithrombin (AT). The high-affinity binding site for AT is a
       specific pentasaccharide sequence that is of low abundance and
       completely absent from the majority of heparin chains. We have examined
       the anti-HIV-1 activity of both conventional and low molecular weight
       heparins fractionated according to affinity for AT. The high- and
       low-affinity fractions, despite differing markedly in anticoagulant
       activity, are identical in their ability to bind to the envelope
       glycoprotein of HIV-1, and in their inhibitory effect on HIV-1
       replication in vitro (EC50 1 and 8 micrograms/ml for conventional and
       low molecular weight fractions, respectively). Our study shows that the
       anti-HIV activity of heparin is independent of its antithrombin-mediated
       inhibition of coagulation proteases. Therefore, heparin preparations
       retaining full anti-HIV-1 activity in vitro but with greatly reduced
       anticoagulant activity may be readily produced for further clinical
       investigation in the prophylaxis and therapy of HIV infection.
 DE    Anticoagulants/*PHARMACOLOGY  Antithrombin III/METABOLISM  Antiviral
       Agents/CHEMISTRY/*PHARMACOLOGY  Cell Line
       Heparin/CHEMISTRY/*PHARMACOLOGY  Human  HIV-1/*DRUG EFFECTS/PHYSIOLOGY
       Molecular Weight  Structure-Activity Relationship  Support, Non-U.S.
       Gov't  Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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