alexa Broad spectrum inhibition of HIV-1 infection by sulfated K5 Escherichia coli polysaccharide derivatives.
Biomedical Sciences

Biomedical Sciences

Journal of Bioengineering & Biomedical Science

Author(s): Vicenzi E, Gatti A, Ghezzi S, Oreste P, Zoppetti G,

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Abstract OBJECTIVE: HIV-1 entry into CD4 cells represents a main target for developing novel antiretroviral agents and microbicides. DESIGN: Sulfated derivatives of the K5 polysaccharide have a backbone structure resembling the heparin precursor, but are devoid of the anticoagulant activity. The derivatives were chemically sulfated in the N position after N-deacetylation, in the O position, or in both sites. METHODS: HIV replication in human T cell blasts, monocyte-derived macrophages and cell lines was studied in the presence of sulfated K5 derivatives. RESULTS: O-sulfated [K5-OS(H)] and N,O-sulfated [K5-N,OS(H)] K5 derivatives with high degree of sulfation inhibited the replication of an HIV strain using CXCR4 as entry co-receptor (X4 virus) in both cell lines and T-cell blasts. K5 derivatives also strongly inhibited the multiplication of CCR5-dependent HIV (R5 virus) in cell lines, T-cell blasts and primary monocyte-derived macrophages. Their 50\% inhibitory concentration was between 0.07 and 0.46 microM, without evidence of cytotoxicity even at the maximal concentration tested (9 microM). In addition, both K5-N,OS(H) and K5-OS(H) potently inhibited the replication of several primary HIV-1 isolates in T-cell blasts, with K5-N,OS(H) being more active than K5-OS(H) on dual tropic R5X4 strains. K5 derivatives inhibited the early steps of virion attachment and/or entry. CONCLUSIONS: Because K5 derivatives are unlikely to penetrate into cells they may represent potential topical microbicides for the prevention of sexual HIV-1 transmission. This article was published in AIDS and referenced in Journal of Bioengineering & Biomedical Science

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