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02225 ANTI-HIV AND OTHER STD PATHOGEN ACTIVITIES OF A COMBINATIONAL MICROBICIDE CANDIDATE, PL40 Yang, Jing1, 2 Combinational microbicide targets at two or more sites in fighting against HIV-1 infection and is expected to be more powerful than single compound. We designed a combinational microbicide candidate, PL40, which is composed of PS20 and LN43. PS20 with high anti-HIV activity is a plant-derived polysaccharide sulfate, and was reported in the last conference (A017). LN43 is a rare earth compound with small molecular weight. The anti-HIV activity of LN43 was detected by syncytial formation inhibition assay for HIV?B and by p24 ELISA assay for R5 strain (HIVAda-M), and its effective concentration (EC50) was 23.0 mg/ml and 23.8 mg/ml, and its therapeutic index?TI?was 97 and 76, respectively. EC50 of PS20 in anti-HSV activity detected by plaque reduction assay was 68 mg/ml. The minimum inhibition concentration (MIC) of LN43 defined as &Mac179; 90? inhibition compared to growth control was 1.17 mg/ml for Candida albicans using an improved MTT test. Both compounds had no inhibition activity for either Neisseria gonorrhoeae or Ureaplasma urealyticum. The time-of-addition experiment showed that both compounds may target at early stage (binding/fusion) of HIV-1 replicate cycle. Furthermore, when combined usage of PS20 with LN43 at concentration ratios of 1:1, 1:4 and 1:11 and at ECs50, 70 and 90, their means of anti-HIV-1 combination indeces (CIs) measured using mixed dose effect analyses and the CalcuSyn package were less than 0.5, and the strong synergism was shown. Postgraduate student, Jing Yang |
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