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Information × Registration Number 0225U000499, (0123U101371) , R & D reports Title Prediction of bioactivity and development of modern approaches to the synthesis of heterocyclic compounds for the needs of the pharmaceutical industry. Chapter 3. In vitro and in vivo study of antiviral activity of synthesized compounds against influenza viruses, adenovirus and SARS-CoV-2 model systems popup.stage_title Проведення in vivo доклінічних досліджень токсичності та антивірусної активності сполук, селектованих методом in silico та in vitro. Head Zahorodnia Svitlana D., Кандидат біологічних наук Registration Date 13-01-2025 Organization Institute of Microbiology and Virology named after D. K. Zabolotny of the National Academy of Sciences of Ukraine popup.description1 In vitro selection of potential drug candidates with antiviral activity selected in silico and in vivo preclinical studies of their toxicity and antiviral activity. popup.description2  Within the framework of this work, an in vitro and in silico analysis of cytotoxicity and antiviral activity of newly synthesized low-molecular compounds was performed. Their pharmacokinetic parameters were analyzed, the compounds has a favorable profile of physicochemical parameters and comply with Lipinski's rules, while their predicted toxicity indicators varied depending on the structure. The CC50 values of the compounds were in the range of 224-5000 μg/ml, depending on the cell culture and surface functional groups in their composition. "Leader structures" were identified, characterized by a high level of inhibitory activity and greater selectivity towards human adenovirus type 2. Depending on the concentration, compounds 1753, 1784, 1779 and 1792 (thiadiazine derivatives) reduced adenovirus reproduction by 50-79%. However, only compound 1779 completely blocked the formation of fully infectious adenovirus progeny. Among the fluorinated diastereomers and thiadiazine derivatives, compounds that actively inhibit the reproduction of influenza A virus have been identified. Their molecular docking showed that substances 10S-46 and 1870 are highly likely inhibitors of the cap-binding activity of RNA-dependent RNA polymerase. Molecular docking of the compounds revealed that only 1794 could inhibit the interaction of the RBD of the viral S-glycoprotein with human ACE2. However, this activity was not confirmed using the competitive ELISA method. The acute toxicity of the compounds in mice was studied, hematological and biochemical blood parameters were determined, and the LD50 of the compounds was mesured, which indicate their safety for the cardiovascular and excretory systems of the animal. Thus, the obtained in vitro, in silico and in vivo data on the activity of the compounds indicate that diastereomers and thiadiazine derivatives are new promising molecular scaffolds for the development of potential antiviral and antitumor agents. Product Description popup.authors Artiukh Liubov O. Baranova Halyna V. Zaremba Andrii A. Zaremba Polina Yu. Zelena Liubov B. Povnytsia Olha Yu. Tkachenko Nina Yu. Shchytinina Hanna S. popup.nrat_date 2025-01-13 Close