Rational Approach toward COVID-19’s Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis
Ruan Sousa Bastos, Christiane P. O. Aguiar, Jorddy Neves Cruz, Ryan da Silva Ramos, Njogu Mark Kimani, João Sammy Nery de Souza, Mariana Helena Chaves, Humberto Fonseca de Freitas, Samuel Silva da Rocha Pita, Cleydson B. R. Santos · International Journal of Molecular Sciences · 2024
This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from −6.2 to −9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein–ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.