Qualitative and quantitative analysis of anti-viral compounds against SARS-CoV-2 protease enzyme by molecular dynamics simulation and MM/PBSA method

Background: A significant worry for global public health is the international spread of the coronavirus disease-19 triggered through the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Herein, an attempt was performed to qualitative and quantitative analysis of a series of compounds against SARS-CoV-2 main protease (M<[pro]) by in silico studies. Methods: About one hundred anti-viral compounds were collected from DrugBank database. In the second stage, molecular docking simulation was carried out to identify interactions of the molecules with the key residues in the M<[pro] active site. Finally, the molecular dynamics simulation of four top-ranked compounds and X77 as Co-crystal ligand were investigated. Results:Based on molecular docking studies, four compounds DB00224, DB00220, DB01232 and DB08873 exhibited the best results among compounds against M<[pro] enzyme. Additionally, molecular dynamic simulation and free binding energy were accomplished to compute the interaction energies and stability of the top-ranked compounds at the active site. The binding energy portions of the compounds into the enzyme active site exposed that Van der Waals and non-polar interactions were fundamental factors in the molecule binding. The ligand connections were steadied via hydrophobic interactions and several key hydrogen bonds especially with Glu166 and His41 residues into the active site. Conclusion: According to calculations of docking and MD, it was observed that the active site is mostly hydrophobic, where the value of the ∆Evdw is higher than that of the ∆Eele. Additionally, the results showed the steady of selected ligands binding with SARS-CoV-2 M<[pro] active site.