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Information × Registration Number 0225U005028, (0125U002921) , R & D reports Title Study of the topological features of the functional surface of SARS-CoV-2 life cycle factors for their potential to interact with low-molecular-weight chemical compounds popup.stage_title Дослідження топологіxних особливостей ACE2-зв'язуючої ділянки RBD варіанту Омікрон B.1.1.529 SARS-CoV-2 Head Zaremba Andrii A., Registration Date 24-12-2025 Organization Institute of Microbiology and Virology named after D. K. Zabolotny of the National Academy of Sciences of Ukraine popup.description1 To investigate the ACE2-binding site of the receptor binding domain of the S-glycoprotein and the active site of the main protease of SARS-CoV-2 using molecular modeling for the presence of pockets and the degree of their suitability for stable interaction with a low-molecular-weight ligand as a potential drug. popup.description2 The goal of the work at this stage was to study the topological features of the RBD ACE2-binding site of the SARS-CoV-2 variant Omicron B.1.1.529. In accordance with the goal, the following was carried out during the reporting period: 1. Preparation of input data and preliminary filtering of the library of FDA-approved drug compounds based on molecular weight. 2. Virtual screening of the library of FDA-approved drug compounds for their interaction with the RBD ACE2-binding site of the SARS-CoV-2. 3. Selection of molecules with increased potential for interaction with the RBD in the area of ​​interest. Simulation of their molecular dynamics (50ns) in complex with the target. 4. Analysis of the stability of the selected complexes and selection of several compounds with the highest probability of complex formation.Their extended simulation study (200ns) in complex with RBD. Calculation of the binding free energy by the MM/PBSA method. 5. In vitro study of the potential of ketodarolutamide as a competitive inhibitor of RBD. 6. Processing of the obtained results and creation of a general map of the surface topology of the Omicron B.1.1.529 RBD. As a result: 1. It was determined that ketodarolutamide in simulation experiments is capable of stable interaction with the RBD of SARS-CoV-2 variant Omicron B.1.1.529 in the ACE2-binding site. The energy gain due to complexation, in this case, was -11.33±3.41 kcal/mol. 2. It was confirmed in vitro (via ELISA) that this antiandrogen is capable of counteracting the interaction of the SARS-CoV-2 RBD with human ACE2. Although to a degree that does not allow us to state its high potential as an anti-COVID agent, it allows its use as a scaffold structure for further studies by other research groups. 3. A map of the surface topology of the Omicron B.1.1.529 RBD was created and an additional pocket located outside the ACE2-binding site of this factor was identified, which is suitable for interaction with a small ligand. Product Description popup.authors Polina Y. Zaremba Andrii A. Zaremba popup.nrat_date 2025-12-24 Close