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Information × Registration Number 0224U032603, (0123U102849) , R & D reports Title Molecular design, synthesis and screening of new potential antiviral pharmaceutical ingredients for the treatment of infectious diseases COVID-19 popup.stage_title Молекулярний скринінг та 3D-фармакофорний докінг віртуальних бібліотек нових сполук, структурна оптимізація молекул-хітів, генерація бібліотек оптимізованих структур та in silico оцінка їх активності як інгібіторів протеаз коронавірусу.Молекулярно-динамічне моделювання системи “молекула-хіт – протеаза SARSCoV-2”, розробка шляхів синтезу найбільш перспективних молекул-хітів з потенційною коронавірусною активністю, їх синтез, визначення чистоти та доведення хімічної будови Head Kaluhin Oleh M., к.х.н. Registration Date 26-11-2024 Organization V.N. Karazin Kharkiv National University popup.description1 The project aims to develop pharmacophore, molecular-dynamic models, generate de novo chemical space according to the DAECS algorithm, and carry out screening for new inhibitors of SARS-CoV-2 virus proteases. Based on the mechanisms of specific binding of Mpro and PLpro proteases to ligands, design dual-acting inhibitors that are promising for developing anticoronavirus drugs and synthesize hit-molecules taking into account ADMET parameters, and, finally, determine their activity in vitro. popup.description2  The research object: new Mpro and PLpro SARS-CoV-2 protease inhibitor molecules, including dual action, ligand-receptor interactions of the molecule-hit complex – SARS-CoV-2 virus protease, methods of synthesis of the latest structures for the development of anti-coronavirus drugs. The research subject: molecular design, screening, 3D docking of new molecules-inhibitors of viral proteases, including dual-acting ones aimed at blocking specific proteases of the SARS-CoV-2 virus, in silico assessment of their activity, molecular-dynamic modeling of "molecule-hit" systems – SARS-CoV-2 protease in the liquid phase", retrosynthetic analysis, pathfinding and development of techniques for the synthesis of hit molecules for further research aimed at discovering drugs for COVID-19. The work purpose is the development of pharmacophore, molecular dynamic models, the generation of de novo chemical space and screening for new protease inhibitors of the SARS-CoV-2 virus; carrying out the molecular design of dual action inhibitors taking into account the mechanisms of specific binding to Mpro and PLpro proteases; selection of lead compounds that are promising for the creation of anti-coronavirus drugs taking into account ADMET parameters; synthesis of leader molecules. The research methodology is based on computer methods of spatial structure prediction, receptor-ligand interaction analysis, the use of QSAR/QSPR approaches, discriminant analysis and the logistic regression method for the analysis of structures, molecular descriptors and active fragments, on methods of creating 3D pharmacophore and all-atom molecular dynamic models and QSAR models; on algorithms for generating de novo chemical space, receptor-oriented docking, methods of retrosynthetic analysis, methods of organic synthesis, development of methods of synthesis of new promising hit molecules, methods of instrumental analysis.   Product Description popup.authors Yevsieieva Larysa V. Ivanov Volodymyr V. Heleveria Anna O. Zakharov Anton B. Kaluhin Oleh M. Kyrychenko Oleksandr V. Kovalenko Serhii M. Kolesnik Yaroslav V. Lohacheva Kateryna O. Trostianko Pavlo V. popup.nrat_date 2024-11-26 Close