Virtual Screening of Phytochemicals as Potential Inhibitors of SARS-CoV-2 Main Protease Enzyme.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronaviruses that emerged in China at Wuhan city, Hubei province during December 2019. Subsequently, SARS-CoV-2 has spread worldwide and caused millions of deaths around the globe. Several compounds and vaccines have been proposed to tackle this crisis. Novel recommended in silico approaches have been commonly used to screen for specific SARS-CoV-2 inhibitors of different types. Herein, the phytochemicals of Pakistani medicinal plants (especially ) were virtually screened to identify potential inhibitors of the SARS-CoV-2 main protease enzyme. The X-ray crystal structure of the main protease of SARS-CoV-2 with an inhibitor was obtained from the protein data bank while phytochemicals were retrieved from different drug databases. The docking technique was carried out to assess the binding efficacy of the retrieved phytochemicals; the docking results revealed that several phytochemicals have potential to inhibit the SARS-CoV-2 main protease enzyme. Among the total docked compounds, the docked complexes were considered for further study and evaluated for their physiochemical and pharmacokinetic properties. The docked complexes with the best binding energies were as follows: the docked complex with a -7 kcal/mol binding energy score, the docked complex with a -6.9 kcal/mol binding energy score, and the docked complex with a -6.8 kcal/mol binding energy score. These complexes were subjected to a molecular dynamic simulation analysis for further validation to check the dynamic behavior of the selected top-complexes. During the whole simulation time, no major changes were observed in the docked complexes, which indicated complex stability. Additionally, the free binding energies for the selected docked complexes were also estimated via the MM-GB/PBSA approach, and the results revealed that the total delta energies of MMGBSA were -24.23 kcal/mol, -26.38 kcal/mol, and -25 kcal/mol for , and , respectively. MMPBSA calculated the delta total energy as -17.23 kcal/mol ( complex), -24.75 kcal/mol ( complex), and -24.86 kcal/mol ( complex). This study explored in silico screened phytochemicals against the main protease of the SARS-CoV-2 virus; however, the findings require an experimentally based study to further validate the obtained results.