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

Author First name, Last name, Institution

Rashi Srivastava, Dr. A.P.J. Abdul Kalam Technical University
Shubham Tripathi, Dr. A.P.J. Abdul Kalam Technical University
Sreepoorna Unni, Zayed University
Arif Hussain, Manipal Academy of Higher Education
Shafiul Haque, Jazan University
Nandita Dasgupta, Dr. A.P.J. Abdul Kalam Technical University
Vineeta Singh, Dr. A.P.J. Abdul Kalam Technical University
Bhartendu Nath Mishra, Dr. A.P.J. Abdul Kalam Technical University

ORCID Identifiers

0000-0002-9679-767X

0000-0002-1478-338X

0000-0002-0851-4845

0000-0002-2989-121X

0000-0003-1850-7443

0000-0001-6787-8203

0000-0003-3191-406X

Document Type

Article

Source of Publication

Current pharmaceutical design

Publication Date

12-10-2020

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.

DOI Link

10.2174/1381612826666201210122726

ISSN

1381-6128

Publisher

Bentham Science Publishers B.V.

Volume

26

Last Page

16

Disciplines

Medicine and Health Sciences

Keywords

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

Scopus ID

85103544515

Recommended Citation

Srivastava, Rashi; Tripathi, Shubham; Unni, Sreepoorna; Hussain, Arif; Haque, Shafiul; Dasgupta, Nandita; Singh, Vineeta; and Mishra, Bhartendu Nath, "Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies" (2020). All Works. 3095.
https://zuscholars.zu.ac.ae/works/3095

Indexed in Scopus

yes

Open Access

no