tetano
Editor, Senior Moderator
Curr Pharm Des
. 2020 Dec 10.
doi: 10.2174/1381612826666201210122726. Online ahead of print.
Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies
Rashi Srivastava[SUP] 1 [/SUP], Shubham Tripathi[SUP] 1 [/SUP], Sreepoorna Unni[SUP] 2 [/SUP], Arif Hussain[SUP] 3 [/SUP], Shafiul Haque[SUP] 4 [/SUP], Nandita Dasgupta[SUP] 1 [/SUP], Vineeta Singh[SUP] 1 [/SUP], Bhartendu Nath Mishra[SUP] 1 [/SUP]
Affiliations
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
E: -10.47 kcal/mol; 6W41E: -10.96 kcal/mol) and Cianidanol (6YB7E: -8.85 kcal/mol; 6Y84E:-10.02 kcal/mol; 6LXTE:-9.36 kcal/mol; 6W41E: -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; Cianidanol; Fiboflavin; Mpro; SARS-CoV-2; Silybin B; Spike Protein.
. 2020 Dec 10.
doi: 10.2174/1381612826666201210122726. Online ahead of print.
Silybin B and Cianidanol Inhibit M pro and Spike Protein of SARS-CoV-2: Evidence from in Silico Molecular Docking Studies
Rashi Srivastava[SUP] 1 [/SUP], Shubham Tripathi[SUP] 1 [/SUP], Sreepoorna Unni[SUP] 2 [/SUP], Arif Hussain[SUP] 3 [/SUP], Shafiul Haque[SUP] 4 [/SUP], Nandita Dasgupta[SUP] 1 [/SUP], Vineeta Singh[SUP] 1 [/SUP], Bhartendu Nath Mishra[SUP] 1 [/SUP]
Affiliations
- PMID: 33302853
- DOI: 10.2174/1381612826666201210122726
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
E: -10.47 kcal/mol; 6W41E: -10.96 kcal/mol) and Cianidanol (6YB7E: -8.85 kcal/mol; 6Y84E:-10.02 kcal/mol; 6LXTE:-9.36 kcal/mol; 6W41E: -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; Cianidanol; Fiboflavin; Mpro; SARS-CoV-2; Silybin B; Spike Protein.