Silybin B and Cianidanol Inhibit M^pro and Spike Protein of SARS-CoV-2: Evidence from in silico Molecular Docking Studies

Title:Silybin B and Cianidanol Inhibit M^pro and Spike Protein of SARS-CoV-2: Evidence from in silico Molecular Docking Studies

Volume: 27 Issue: 32

Author(s): Rashi Srivastava, Shubham Tripathi, Sreepoorna Unni, Arif Hussain, Shafiul Haque, Nandita Dasgupta, Vineeta Singh*Bhartendu N. Mishra*

Affiliation:

• Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow- 226021, Uttar Pradesh,India

• Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow- 226021, Uttar Pradesh,India

Keywords: COVID-19, SARS-CoV-2, M^pro, spike protein, silybin B, cianidanol, fiboflavin.

Abstract:

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 M^pro 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 M^pro (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 M^pro 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 forces.

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.

Cite this article as:

Srivastava Rashi , Tripathi Shubham , Unni Sreepoorna , Hussain Arif , Haque Shafiul , Dasgupta Nandita , Singh Vineeta *, Mishra N. Bhartendu *, Silybin B and Cianidanol Inhibit M^pro and Spike Protein of SARS-CoV-2: Evidence from in silico Molecular Docking Studies, Current Pharmaceutical Design 2021; 27 (32) . https://dx.doi.org/10.2174/1381612826666201210122726