Silybin B and Cianidanol Inhibit Mpro and Spike Protein of SARS-CoV-2 : Evidence from in silico Molecular Docking Studies
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:27 |
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| Enthalten in: |
Current pharmaceutical design - 27(2021), 32 vom: 02., Seite 3476-3489 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Srivastava, Rashi [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.10.2021 Date Revised 18.10.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1381612826666201210122726 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM318682176 |
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| 100 | 1 | |a Srivastava, Rashi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Silybin B and Cianidanol Inhibit Mpro and Spike Protein of SARS-CoV-2 |b Evidence from in silico Molecular Docking Studies |
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| 500 | |a Date Completed 18.10.2021 | ||
| 500 | |a Date Revised 18.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a COVID-19 | |
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| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a cianidanol | |
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| 700 | 1 | |a Singh, Vineeta |e verfasserin |4 aut | |
| 700 | 1 | |a Mishra, Bhartendu N |e verfasserin |4 aut | |
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