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02503 K5 POLYSACCHARIDE DERIVATIVE: POTENTIAL CANDIDATE MICROBICIDE FOR PREVENTION OF HIV-1 INFECTION Vicenzi, Elisa* We have previously described that a derivative of Escherichia Coli K5 polysaccharide with high degree of sulfation [K5-N,OS(H)] inhibits HIV-1 attachment and/or entry (AIDS 17, 177-181, 2003). Here we have investigated the potential inhibitory effects of K5-N,OS(H) on the replication of several primary HIV isolates. In addition we have tested the efficacy of K5-N,OS(H) in preventing dendritic cells (DC)-mediated infection of peripheral blood mononuclear cells (PBMC). K5-N,OS(H) potently inhibited the replication of all (30 out of 30) tested primary HIV isolates including 16 R5, 4 X4 and 10 R5X4 viruses in T cell blasts. The 50% inhibitory concentration (IC50) was 2.1± 1.6 µg/ml, without evidence of cytotoxicity even at the maximal concentration tested (100 µg/ml). K5-N,OS(H) (100 µg/ml) abolished R5 HIV replication in either DC cultivated alone or in DC-PBMC co-cultures. X4 HIV replication was only detected in DC-PBMC co-cultures and it was also suppressed by this concentration of K5-N,OS(H). In conclusion, the K5-N,OS(H) antiviral activity against several primary HIV-1 isolates with different coreceptor usage in both T cell blasts, DC, and DC-mediated PBMC infection coupled with the lack of penetration into cells, render this molecule a potential candidate as a topical microbicide for preventing sexual HIV-1 transmission. Dr Elisa Vicenzi |
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