LOW ANTICOAGULANT HEPARIN RETAINS ANTI-HIV TYPE-1 ACTIVITY IN-VITRO

Heparin is a potent inhibitor of HIV-1 replication, in addition to bei ng a well-established inhibitor of blood coagulation. The major antico agulant activity of heparin results from binding to the plasma protein antithrombin (AT). The high-affinity binding site for AT is a specifi c pentasaccharide sequence that is of low abundance and completely abs ent from the majority of heparin chains. We have examined the anti-HIV -1 activity of both conventional and low molecular weight heparins fra ctionated according to affinity for AT. The high- and low-affinity fra ctions, despite differing markedly in anticoagulant activity, are iden tical in their ability to bind to the envelope glycoprotein of HIV-1, and in their inhibitory effect on HIV-1 replication in vitro (EC(50) 1 and 8 mu g/ml for conventional and low molecular weight fractions, re spectively). Our study shows that the anti-HIV activity of heparin is independent of its antithrombin-mediated inhibition of coagulation pro teases. Therefore, heparin preparations retaining full anti-HIV-1 acti vity in vitro but with greatly reduced anticoagulant activity may be r eadily produced for further clinical investigation in the prophylaxis and therapy of HIV infection.