Background: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2) play a major role in viral infection development by producing several
non-structural proteins (nsPs) and penetrating the host cells, respectively. In this study, the potential of in silico
molecular docking-based drug repositioning approach was exploited for identifying the inhibitors of Mpro and
SP of SARS-CoV-2.
Methods: A total of 196 compounds, including various US-FDA-approved drugs, vitamins, and their analogs,
were docked with Mpro (PDB IDs: 6YB7 and 6Y84), and the top six ligands were further tested for ADME
properties, followed by docking with SP (PDB IDs: 6LXT and 6W41).
Results: Out of 196 compounds, binding energy (DE) of Silybin B (6YB7: DE: -11.20 kcal/mol; 6Y84: DE: -
10.18 kcal/mol; 6LXT: DE: -10.47 kcal/mol; 6W41: DE: -10.96 kcal/mol) and Cianidanol (6YB7: DE: -8.85
kcal/mol; 6LXT: DE: -9.36 kcal/mol; 6Y84: DE: -10.02 kcal/mol; 6W41: DE: -9.52 kcal/mol) demonstrated
better binding and ADME properties compared with the currently endeavored drugs like Hydroxychloroquine
and Lopinavir. Additionally, Elliptinone, Diospyirin, SCHEMBL94263, and Fiboflavin have shown encouraging
results. Fiboflavin, an immunity booster, was found to inhibit both the Mpro and spike protein of SARSCoV-
2. It was observed that amino acid residues MET6, ALA7, PHE8, PRO9, ASP295, GLY302, VAL303,
and THR304 play significant roles in protein-ligand interactions through hydrogen bonds and Vander Waals
Conclusion: Silybin B and Cianidanol showed excellent binding and ADME properties compared with the currently
endeavored drugs and can be exploited as therapeutic options against SARS-CoV-2 infection after experimental
validation and clinical trials.