Submit Manuscript  

Article Details


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

Author(s):

Rashi Srivastava, Shubham Tripathi, Sreepoorna Unni, Arif Hussain, Shafiul Haque, Nandita Dasgupta, Vineeta Singh* and Bhartendu Nath Mishra*   Pages 1 - 14 ( 14 )

Abstract:


Background: The main proteases (Mpro) and Spike Proteins (SP) of Severe Acute Respiratory Syndrome Coronavirus 2 (SARSCoV-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; 6Y84:DE:-10.02 kcal/mol; 6LXT:DE:-9.36 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 SARS-CoV-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.

Keywords:

COVID-19, SARS-CoV-2, Mpro, Spike Protein, Silybin B, Cianidanol, Fiboflavin

Affiliation:

Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh, Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh, Department of Life and Environmental Sciences, College of Natural & Health, Zayed University, P.O. Box 19282, Dubai, School of Life Sciences, Manipal Academy of Higher Education, P.O. Box 345050, Dubai, Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan-45142, Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh, Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh, Department of Biotechnology, Institute of Engineering and Technology, Dr. A.P.J. Abdul Kalam Technical University, Lucknow-226021, Uttar Pradesh



Read Full-Text article