Abstract:

Background. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has one of the largest genomes. It encodes 16 non-structural proteins that are necessary for replicating and overcoming host defense mechanisms. Flavonoids are of interest as research objects in developing drugs for comprehensive COVID-19 therapy. This group of compounds is characterized by a wide range of biological activity and a high safety profile. Aim. To perform virtual screening of flavonoids for possible inhibition of proteins of the SARS-CoV-2 infection. Materials and methods. Structural proteins of SARS-CoV-2 infection, such as ADP-binding domain NSP3, main protease NSP5, RNA-dependent RNA-polymerase NSP12, and endoribonuclease NSP15, were obtained from Protein Data Bank (PDB). Flavonoid structures were obtained from the ZINC database. Protein models were processed using AutoDockTools software, and ligands were processed in Raccoon | AutoDock VS. Virtual screening and re-docking were performed in AutoDock Vina. Results. Validation showed agreement between native and re-docked conformations, indicating the applicability of the virtual screening method. Flavonoids interacted with the key amino acid residues in all the studied proteins. The highest binding energy was demonstrated by 3,7-dihydroxyflavone and 6S-coccineone B, the latter having a multimodal effect. Conclusion. The results of the study may be used for the development of phytomedicines for comprehensive therapy for COVID-19.

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