Silybin b and cianidanol inhibit Mpro and spike protein of SARS-CoV-2: Evidence from in silico molecular docking studies

Rashi Srivastava; Shubham Tripathi; Sreepoorna Unni; Arif Hussain; Shafiul Haque; Nandita Dasgupta; Vineeta Singh; Bhartendu N. Mishra

doi:10.2174/1381612826666201210122726

Silybin b and cianidanol inhibit M^pro and spike protein of SARS-CoV-2: Evidence from in silico molecular docking studies

Rashi Srivastava, Shubham Tripathi, Sreepoorna Unni, Arif Hussain, Shafiul Haque, Nandita Dasgupta, Vineeta Singh^*, Bhartendu N. Mishra^*

^*Corresponding author for this work

Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Background: The main proteases (M^pro) 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.

Original language	English
Pages (from-to)	3476-3489
Number of pages	14
Journal	Current pharmaceutical design
Volume	27
Issue number	32
Early online date	10 Dec 2020
DOIs	https://doi.org/10.2174/1381612826666201210122726
Publication status	Published - 2021

Bibliographical note

Funding Information:
All India Council for Technical Education (AICTE), Government of India for providing financial support (scholarship to RS) for this study (Grant no. 2/3/13/1440).The authors RS, ST, VS, ND, and BNM are grateful to the Institute of Engineering & Technology, Dr. APJ Abdul Kalam Technical University, Lucknow (UP), India, for providing the necessary laboratory facility for this study. The author R.S. acknowledges the All India Council for Technical Education (AICTE), Government of India, for providing financial support (scholarship) for this study. SH sincerely acknowledges Jazan University for providing access to the Saudi Digital Library for this study.

Publisher Copyright:
© 2021 Bentham Science Publishers.

Keywords

Cianidanol
COVID-19
Fiboflavin
M
SARS-CoV-2
Silybin B
Spike protein

ASJC Scopus subject areas

Pharmacology
Drug Discovery

Access to Document

10.2174/1381612826666201210122726

Cite this

@article{8d3f67e400cc4cbe91ce1859a056ddd5,

title = "Silybin b and cianidanol inhibit Mpro and spike protein of SARS-CoV-2: Evidence from in silico molecular docking studies",

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 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 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 = "Cianidanol, COVID-19, Fiboflavin, M, SARS-CoV-2, Silybin B, Spike protein",

author = "Rashi Srivastava and Shubham Tripathi and Sreepoorna Unni and Arif Hussain and Shafiul Haque and Nandita Dasgupta and Vineeta Singh and Mishra, {Bhartendu N.}",

note = "Funding Information: All India Council for Technical Education (AICTE), Government of India for providing financial support (scholarship to RS) for this study (Grant no. 2/3/13/1440).The authors RS, ST, VS, ND, and BNM are grateful to the Institute of Engineering & Technology, Dr. APJ Abdul Kalam Technical University, Lucknow (UP), India, for providing the necessary laboratory facility for this study. The author R.S. acknowledges the All India Council for Technical Education (AICTE), Government of India, for providing financial support (scholarship) for this study. SH sincerely acknowledges Jazan University for providing access to the Saudi Digital Library for this study. Publisher Copyright: {\textcopyright} 2021 Bentham Science Publishers.",

year = "2021",

doi = "10.2174/1381612826666201210122726",

language = "English",

volume = "27",

pages = "3476--3489",

journal = "Current pharmaceutical design",

issn = "1381-6128",

publisher = "Bentham Science Publishers",

number = "32",

}

TY - JOUR

T1 - Silybin b and cianidanol inhibit Mpro and spike protein of SARS-CoV-2

T2 - Evidence from in silico molecular docking studies

AU - Srivastava, Rashi

AU - Tripathi, Shubham

AU - Unni, Sreepoorna

AU - Hussain, Arif

AU - Haque, Shafiul

AU - Dasgupta, Nandita

AU - Singh, Vineeta

AU - Mishra, Bhartendu N.

N1 - Funding Information: All India Council for Technical Education (AICTE), Government of India for providing financial support (scholarship to RS) for this study (Grant no. 2/3/13/1440).The authors RS, ST, VS, ND, and BNM are grateful to the Institute of Engineering & Technology, Dr. APJ Abdul Kalam Technical University, Lucknow (UP), India, for providing the necessary laboratory facility for this study. The author R.S. acknowledges the All India Council for Technical Education (AICTE), Government of India, for providing financial support (scholarship) for this study. SH sincerely acknowledges Jazan University for providing access to the Saudi Digital Library for this study. Publisher Copyright: © 2021 Bentham Science Publishers.

PY - 2021

Y1 - 2021

N2 - 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 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.

AB - 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 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.

KW - Cianidanol

KW - COVID-19

KW - Fiboflavin

KW - M

KW - SARS-CoV-2

KW - Silybin B

KW - Spike protein

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DO - 10.2174/1381612826666201210122726

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SN - 1381-6128

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