The SARS-Cov-2 Proliferation Blocked by a Novel and Potent Main Protease Inhibitor via Computer-aided Drug Design

Abstract

The recent prevalence of novel “coronavirus disease 2019” has expanded quickly globally, causing a universal pandemic. Herein, an effort was constructed to design a potent drug to inhibit the main protease of SARS-Cov-2 (3CLp) by means of structure-based drug design. A large library of the compounds was used for virtual screening. After molecular docking and ADME studies, we selected a compound with a better binding affinity to the 3CLp active site and acceptable ADME properties compared to the selected positive control drug. Molecular dynamic (MD) simulation (200 ns) and Molecular Mechanics–Poisson Boltzmann Surface Area (MM-PBSA) were used for further analysis. MD simulation outcomes have proved that the 3CLp-ZINC31157475 complex possesses a considerable value of dynamic properties such as flexibility, stability, compactness, and binding energy. Our MM-PBSA computation illustrates that ZINC31157475 is more potent (-88.03 kcal mol-1) than nelfinavir (-19.54 kcal mol-1) against COVID-19 3CLp. Further, we have determined that the main residues of the 3CLp interact with ligands from per-residue binding energy. In conclusion, we suggest that ZINC31157475 can potentially treat COVID-19 by inhibition of the 3CLp. However, in-vitro and in-vivo study is essential for approval of this suggestion.