COVID-19 is the last disease caused by SARS-CoV-2 associated with a severe immune response and lung damage. The main protease (Mpro) has a vital role in SARS-CoV-2 proliferation. Moreover, humans lack homologous Mpro, which makes the Mpro a suitable drug target for the development of SARS-CoV-2 drugs. The purchasable L5000 library (Selleckchem Inc) includes 99,040 compounds that were used for virtual screening. After molecular docking and ADME studies, we selected a compound (WAY-604395) with a potent binding affinity to the Mpro active site and acceptable ADME properties compared to the reference drug (nelfinavir). Molecular dynamics (MD) simulation outcomes have proved that the Mpro-WAY604395 complex possesses a considerable value of flexibility, stability, compactness and binding energy. Our Molecular Mechanics Poisson–Boltzmann Surface Area (MM-PBSA) calculation demonstrates that WAY-604395 is more potent (− 272.19 kcal mol − 1 ) in comparison with nelfinavir (− 173.39 kcal mol − 1 ) against SARS-CoV-2 Mpro. In conclusion, we suggest that WAY-604395 has the potential for the treatment of SARS-CoV-2 by inhibition of the Mpro. 1. Computational modeling was performed to investigate the binding effects of WAY-604395 on SARS-CoV-2 main protease. 2. Through molecular docking and molecular dynamics, compound WAY-604395 was selected to inhibit Mpro. 3. ADME analysis showed that WAY-604395 is not prohibited for human use. [ABSTRACT FROM AUTHOR] Copyright of Journal of Computational Biophysics & Chemistry is the property of World Scientific Publishing Company and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Prevention of SARS-CoV-2 Proliferation with a Novel and Potent Main Protease Inhibitor by Docking, ADMET, MM-PBSA, and Molecular Dynamics Simulation