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03206 THE PROGRAM OF THE MICROBICIDE DEVELOPMENT IN RUSSIA Karamov, Edward* RBackground: The creation of topical microbicides against HIV and other sexual diseases pathogens is so important as vaccine development. Today more than 60 microbicide preparations pass clinical trials. They suppose the use of microbicide preparations will result in 1 million of the new HIV cases decrease. The most important part of the microbicide program is the search of novel specific anti-HIV-1 agents. Our investigations were performed to find perspective compounds and their combinations to employ them in topical microbicides which possess the ability to block the HIV transmission on different stages of virus cell interaction. We have studied original compounds from different groups: sulfated chitosanes, humic acids and plant polyphenol derivatives. Methods: anti-viral activity as well the cytotoxicity of compounds was defined using clinical isolates and laboratory adapted HIV-1 strains and human PMBCs (peripheral mononuclear blood cells) and T-lymphoblastoid cell lines. The level of virus reproduction in infected cells was detected with p24 HIV-1 antigen ELISA detection system. Results: Sulfated chitosane derivatives possessed low cytotoxicity and blocked HIV-1 infection in T-cells (ED50 = 0.08-2.0 ?g/ml). The inhibitory effect depended on the localization and the amount of the sulfated groups and saccharide monomer, the type of anionic groups and the charge of molecules. The ED50 values of the humic acid derivatives against HIV-1 laboratory strain and HIV-1 M-tropic AZT-resistant wild-type strain were 0.85 and 3.5 µg/ml respectively, without appearance of any detectible resistance. The most of studied plant polyphenol derivatives possessed strong cytotoxicity. The consideration of the cytotoxicity and inhibitory effect allowed us to choose the number of compounds with the essential selectivity index: IS = 100 - 1000. Conclusions: We found the number of original compounds with high anti-HIV activity and sufficient selectivity indexes, which should be useful for new microbicide preparations. We are going to use new immunomodulator polyoxidoniy for the improving of the microbicide compositions. The leader of immunochemistry group, of Ivanovsky inst. of Virology, PhD, Edward Karamov |
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