INHIBITION OF HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION BY HEPARIN DERIVATIVES

Heparin (Hep) and sulfated polysaccharides (SPs) have been reported to inhibit HIV infection in vitro. In vivo, anticoagulant activity and r educed bioavailability were found to limit the antiviral effects of He p, In this investigation, three nonanticoagulant N-acylated Hep conjug ates [Ol(1:3)Hep, Pal(1:5)Hep, and Pal(1:5)Hep(SO4)] were compared to Hep for their ability to interact with HIV replication in CD4-positive cell lines and PBMCs. Resulfated palmitoyl-Hep [Pal(1:5)Hep(SO4)] exh ibited the strongest anti-HIV effects, For instance, no provirus HIV D NA was detected in the genome of HIV-1-LAI-infected PBMCs treated with this heparin derivative, Cell-to-cell fusion and RT activity were exp lored to explain these differences, Hep and Pal(1:5)Hep(SO4) derivativ e exerted identical effects on cell-to-cell fusion, On the other hand, Pal(1:5)Hep(SO4) displayed the strongest inhibitory effects in the ac ellular RT inhibition assay, This suggests that RT might be a second t arget for N-acylated Hep, even though SP uptake and the preferential e ffects of SPs on RT as opposed to DNA polymerase have not yet been dem onstrated, Nevertheless, considering the anticoagulant, antiviral, and antiinflammatory effects of N-acylated Hep, the N-acylated Hep deriva tives might be excellent candidates as new anti-HIV pharmacological to ols.