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02444 MANNOSE-SPECIFIC PLANT LECTINS AS POTENTIAL HIV MICROBICIDES Balzarini, Jan* A variety of mannose-specific plant lectins selectively inhibit in cell culture the replication of HIV-1 and HIV-2 strains, including virus strains that show resistance to other classes of anti-HIV drugs (EC50: 0.1-1.0 µg/ml). They also prevent syncytium formation between persistently-infected HUT-78/HIV and CEM/HIV cells and uninfected T-lymphocyte cells. Preexposure of the lectins to HIV-1 particles or persistently HIV-infected cells markedly increased the antiviral efficacy of the plant lectins. They interrupt the virus entry process by interfering with the virus envelope glycoprotein gp120. When exposed to escalating plant lectin concentrations, HIV-1 strains with decreased drug sensitivity could be isolated. A variety of amino acid changes were observed at the N-glycosylation sites and/or the serine or threonine residues that are part of the N-glycosylation motif in gp120. The degree of virus-drug resistance correlated with an increasing number of mutated glycosylation sites in gp120. These virus strains kept full sensitivity to other entry inhibitors such as dextran sulphate, bicyclam AMD3100, chicoric acid and enfuvirtide. The plant lectins under investigation were found to be not mitogenic, colorless and stable at lower pH and higher temperature (50°C). In conclusion, the plant lectins represent a well-defined class of anti-HIV drugs with a microbicidal potential and with a novel drug resistance profile different from that of other existing anti-HIV drugs. Jan Balzarini |
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