Search academic texts

Information × Registration Number 0224U000975, 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 Head Zahorodnia Svitlana D., Кандидат біологічних наук Registration Date 15-01-2024 Organization Institute of Microbiology and Virology named after D. K. Zabolotny of the National Academy of Sciences of Ukraine popup.description2  The object is the cytotoxicity and antiviral activity of fluorine-, chlorine- and bromine-containing compounds against human adenovirus, influenza virus and the in silico SARS-Cov-2 model. In vitro and in silico analysis of cytotoxicity and antiviral activity of newly synthesized compounds was carried out. It is shown that the degree of toxic action depends on the structure, surface functional groups, origin and functional features of cells. Structures with a high level of antiviral activity and selectivity were determined. The inclusion of a dichloromethyl group in the third position of the 5,7-dimethyl-4,7-dihydropyrazolo[4,3-e][1,2,4]thiadiazine 1,1-dioxide molecule enhances the anti-adenoviral effect. Among the fluorinated diastereomers, a compound that inhibits influenza type A virus (1792) was identified, promising for further optimization. The in silico analysis showed that the pyrazolthiadiazepine compound stably maintains its position in the hACE2 and RBD interaction site, is characterized by a mean square deviation of this complex close to the optimal one, and has a significant increase in the energy calculated by MMPBSA. method (-20.59 kcal /mol). This indicates its potential against the SARS-CoV-2 virus, in particular, as an inhibitor of the interaction of the receptor-binding domain of the pathogen's S-glycoprotein with the surface of human angiotensin-converting enzyme. Thus, antiviral and antioxidant effects were found among the newly synthesized compounds. These compounds are likely inhibitors of the cap-binding activity of the RNA-dependent RNA polymerase of the influenza virus and the receptor-binding domain of the S-glycoprotein of SARS-CoV-2. The obtained results are important for the development of antiviral and antitumor drugs based on fluorinated nucleosides, research of target substances. Product Description popup.authors Artiukh Liubov Baranova Galina V. Zaremba Andriy A. Zaremba Polina Yu. Povnitsa Olga Tkachenko Nina Shchytinina Hanna popup.nrat_date 2024-01-15 Close