In silico study of medicinal plants with cyclodextrin inclusion complex as the potential inhibitors against SARS-CoV-2 main protease (Mpro) and spike (S) receptor.

The current outbreak of novel coronavirus disease (COVID-19) causes an alarming number of deaths in 221 countries around the world. Nowadays, there is no specific and effective drug regimen for curing COVID-19. Since the COVID-19 pandemic, several medicinal plants with promising results in the previous SARS-CoV could be used to treat SARS-CoV-2 infected patients. This work assesses proven medicinal plants as potential inhibitors against SARS-CoV-2 main protease (Mpro) and spike (S) receptors by employing in silico methods. Molecular docking studies and 3D structure-based pharmacophore modeling were performed to identify the molecular interactions of potential active molecules with the Mpro and (S) receptor of SARS-CoV-2. The drug-likeness and ADME properties were also predicted to support the drug-like nature of the selected active molecules. The results indicated that the most favorable ligand was Terrestriamide with (ΔG: ─8.70 kcal/mol; Ki: 0.417 µM) and (ΔG: ─7.02 kcal/mol; Ki: 7.21 µM) for Mpro and (S) receptor, respectively. Terrestriamide is also supported with a high drug-likeness value and appropriate ADME profile. Furthermore, to improve drug delivery, the cyclodextrin inclusion complex was calculated based on semi-empirical quantum mechanical methods. Terrestriamide/γ-cyclodextrin is the most favorable pathway of inclusion complex formation and could be used to treat COVID-19.