Background: COVID-19 is a global pandemic that caused a dramatic loss of human life worldwide, leading to accelerated research for antiviral drug discovery. Herbal medicine is one of the most commonly used for of alternative medicine for prevention and treatment of many conditions including respiratory system diseases.
Methods: In this study, a computational pipeline was employed, including network pharmacology, molecular docking simulations, and molecular dynamics simulations, to analyze the common phytochemicals of ginger rhizomes and identify candidate constituents as viral inhibitors. Furthermore, experimental assays were performed to analyze the volatile and non-volatile compounds of ginger and to assess the antiviral activity of ginger oil and hydro-alcoholic extract.
Results: Network pharmacology analysis showed that ginger compounds target human genes that are involved in related cellular processes to the viral infection. Docking analysis highlighted five pungent compounds and zingiberenol as potential inhibitors for the main protease (Mpro), spike receptor-binding domain (RBD), and human angiotensin-converting enzyme 2 (ACE2). Finally, (6)-gingerdiacetate was selected for molecular dynamics (MD) simulations as it exhibited the best binding interactions and free energies over the three target proteins. Trajectories analysis of the three complexes showed that RBD and ACE2 complexes with the ligand preserved similar patterns of root mean square deviation (RMSD) and radius of gyration (Rg) values to their respective native structures. These pungent compounds contribute to the higher antiviral activity of ginger extract than HD oil with CC50 of 3.480 μg/ml and IC50 of 2.727 μg/ml.
Conclusion: Our study provides predictive insights that could be useful for development of anti-coronavirus drugs especially (6)-gingerdiacetate that may enhance the host immune response and block RBD binding to ACE2, thereby, inhibiting SARS-CoV-2 infection.