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Design, synthesis and antiviral activity of new cage compoundsтезисы доклада
- Авторы: Klimochkin Y.N., Shiryaev V.A., Leonova M.V., Palyulin V.A., Radchenko E.V.
- Сборник: XX Mенделеевский съезд по общей и прикладной химии, 2016, Abstract book in 5 volumes
- Том: 4
- Тезисы
- Год издания: 2016
- Место издания: XX Mенделеевский съезд по общей и прикладной химии Ekaterinburg Ekaterinburg
- Первая страница: 416
- Последняя страница: 416
- Аннотация: Cage compounds display antiviral activity against a broad spectrum of DNA and RNA viruses. We looked for compounds that are capable to affect orthopoxvirus and influenza A virus proteins. Various orthopoxviruses encode a family of p37 proteins required for packaging and distribution of virions. The structure of p37 protein was found in the UniProt database and it was optimized using molecular dynamics. The best binding site of currently known blockers (tecovirimat and NIOC-14) was then determined. Docking ofabout 100 cage compounds to the best binding site was performed. Anti-influenza activity of adamantane derivatives is based on blocking M2 the ion channel. Different structures of wild type and mutant M2 channels from the RCSBPDB database: 2RLF for WT, 2KIH for S31N, 2KWX for V27A – were used for the search of M2 blockers. Optimization of the structure of proteins was performed by the means of molecular dynamics, potential ligand binding cavities in the dynamic structures of the channel were found. Docking of nearly 800 compounds revealed 52 structures promising as potential inhibitors of mutant S31N and V27A and the wild type M2 channel simultaneously. Based on the docking results a series of new compounds containing cyclic, heterocyclic or arylcarboxamide fragments; polyfunctional adamantane derivatives containing several amino, carboxyl or hydroxyl groups, either directly from the adamantane nucleus or on the periphery of the molecule was synthesized. Testing of antiviral activity was performed in the SSC VB "Vector". Most of the compounds showed pronounced in vitro activity against influenza A viruses (H5N1, H3N2) and orthopox viruses (vaccinia virus, cowpox virus, variola virus, monkeypox virus and ectromelia virus). The work was supported by the RNF, project 15-13-00084.
- Добавил в систему: Радченко Евгений Валерьевич