Molecular docking, molecular dynamics simulation and MM-GBSA studies of the activity of glycyrrhizin relevant substructures on SARS-CoV-2 RNA-dependent-RNA polymerase.

ABSTRACT

SARS-CoV-2 is the causative agent of Coronavirus Disease (COVID-19), which is a life-threatening disease. The World Health Organization has classified COVID-19 as a severe worldwide public health pandemic due to its high death rate, quick transmission, and lack of medicines. To counteract the recurrence of the severe acute respiratory syndrome, active antiviral medications are urgently required. Glycyrrhizin was documented with activity on different viral proteins, including SARS-CoV-2; in this study, the activity of glycyrrhizin and its substructures (604 molecules) were screened on SARS-CoV-2 RNA-dependent-RNA polymerase using molecular docking, molecular dynamic (MD) simulation, and MM/GBSA. Sixteen molecules exhibited docking energy higher than -7 kcal/mol; four compounds (10772603, 101088272, 154730753 and glycyrrhizin) showed the highest binding energy, and good stability during MD simulation. The glycyrrhizin compound exhibited favorable docking energy (-7.9 kcal/mol), and it was the most stable complex during MD simulation. The predicted binding free energy of the glycyrrhizin complex was -57 ± 8 kcal/mol. These findings suggest that this molecule, after more validation, could become a good candidate for developing and manufacturing an anti-SARS-CoV-2 medication.Communicated by Ramaswamy H. Sarma.