Computational analysis of the interactions between Ebselen and derivatives with the active site of the main protease from SARS-CoV-2

In this study, we analyzed the Mpro interaction with EbSe, its analogues, and its metabolites with Cys, GSH, and albumin by molecular docking. We also simulated the electronic structure of the generated molecules by density functional theory (DFT) and explored the stability of EbSe and one of its best derivatives, EbSe-2,5-MeClPh, in the catalytic pocket of Mpro through covalent docking and molecular dynamics. Our results show that EbSe and its analogues bound to GSH/albumin have larger distance between the selenium atom of the ligands and the sulfur atom of Cys145 of Mpro than the other compounds. This suggests that EbSe and its GSH/albumin-analogues may have less affinity for the active site of Mpro. EbSe-2,5-MeClPh was found one of the best molecules, and in molecular dynamics simulations, it showed to undergo more conformational changes in the active site of Mpro, in relation to EbSe, which remained stable in the catalytic pocket. Moreover, this study also reveals that all compounds have the potential to interact closely with the active site of Mpro, providing us with a concept of which derivatives may be promising for in vitro analysis in the future. We propose that these compounds are potential covalent inhibitors of Mpro and that organoselenium compounds are molecules that should be studied for their antiviral properties.PMID:37748316 | DOI:10.1016/j.compbiolchem.2023.107956

Source: Computational Biology and Chemistry - September 25, 2023 Category: Bioinformatics Authors: Guilherme Schmitt Rieder Pablo Andrei Nogara Folorunsho Bright Omage T âmie Duarte Cristiane Lenz Dalla Corte Jo ão Batista Teixeira da Rocha Source Type: research