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.
Keywords: ADMET; COVID-19; DCCM; MM-PBSA; Molecular dynamic; PCA; Protease inhibitors.