Identification of Potential SARS-CoV-2 Main Protease Inhibitors Using Drug Repurposing and Molecular Modeling

Structure-based virtual screening of a molecular library of bioactive compounds was carried out to identify potential inhibitors against SARS-CoV-2 main protease (Mpro), an enzyme critically important for mediating viral replication and transcription. The binding affinity of these compounds to the catalytic site of the enzyme was assessed using molecular docking and molecular dynamics simulations, resulting in six molecules that exhibited high binding affinity to the SARS-CoV-2 Mpro. This is evidenced by the low values of binding free energy of the ligand/Mpro complexes comparable with those predicted using the identical computational protocols for the potent non-covalent SARS-CoV-2 Mpro inhibitor. Based on the data obtained, the identified compounds are supposed to have good therapeutic potential for inhibiting the catalytic activity of the enzyme and form promising basic structures for the development of new effective drugs against SARS-CoV-2 Mpro, an attractive target for anti-COVID-19 agents.