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Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein
The in silico method has provided a versatile process of developing lead compounds from a large database in a short duration. Therefore, it is imperative to look for vaccinations and medications that can stop the havoc caused by SARS-CoV-2. The spike protein of SARS-CoV-2 is required for the viral e...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668477/ https://www.ncbi.nlm.nih.gov/pubmed/36407836 http://dx.doi.org/10.1155/2022/3742318 |
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author | Shrestha, Asmita Marahatha, Rishab Basnet, Saroj Regmi, Bishnu P. Katuwal, Saurav Dahal, Salik Ram Sharma, Khaga Raj Adhikari, Achyut Chandra Basnyat, Ram Parajuli, Niranjan |
author_facet | Shrestha, Asmita Marahatha, Rishab Basnet, Saroj Regmi, Bishnu P. Katuwal, Saurav Dahal, Salik Ram Sharma, Khaga Raj Adhikari, Achyut Chandra Basnyat, Ram Parajuli, Niranjan |
author_sort | Shrestha, Asmita |
collection | PubMed |
description | The in silico method has provided a versatile process of developing lead compounds from a large database in a short duration. Therefore, it is imperative to look for vaccinations and medications that can stop the havoc caused by SARS-CoV-2. The spike protein of SARS-CoV-2 is required for the viral entry into the host cells, hence inhibiting the virus from fusing and infecting the host. This study determined the binding interactions of 36 flavonoids along with two FDA-approved drugs against the spike protein receptor-binding domain of SARS-CoV-2 through molecular docking and molecular dynamics (MD) simulations. In addition, the molecular mechanics generalized Born surface area (MM/GBSA) approach was used to calculate the binding-free energy (BFE). Flavonoids were selected based on their in vitro assays on SARS-CoV and SARS-CoV-2. Our pharmacokinetics study revealed that cyanidin showed good drug-likeness, fulfilled Lipinski's rule of five, and conferred favorable toxicity parameters. Furthermore, MD simulations showed that cyanidin interacts with spike protein and alters the conformation and binding-free energy suited. Finally, an in vitro assay indicated that about 50% reduction in the binding of hACE2 with S1-RBD in the presence of cyanidin-containing red grapes crude extract was achieved at approximately 1.25 mg/mL. Hence, cyanidin may be a promising adjuvant medication for the SARS-CoV-2 spike protein based on in silico and in vitro research. |
format | Online Article Text |
id | pubmed-9668477 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-96684772022-11-17 Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein Shrestha, Asmita Marahatha, Rishab Basnet, Saroj Regmi, Bishnu P. Katuwal, Saurav Dahal, Salik Ram Sharma, Khaga Raj Adhikari, Achyut Chandra Basnyat, Ram Parajuli, Niranjan Adv Pharmacol Pharm Sci Research Article The in silico method has provided a versatile process of developing lead compounds from a large database in a short duration. Therefore, it is imperative to look for vaccinations and medications that can stop the havoc caused by SARS-CoV-2. The spike protein of SARS-CoV-2 is required for the viral entry into the host cells, hence inhibiting the virus from fusing and infecting the host. This study determined the binding interactions of 36 flavonoids along with two FDA-approved drugs against the spike protein receptor-binding domain of SARS-CoV-2 through molecular docking and molecular dynamics (MD) simulations. In addition, the molecular mechanics generalized Born surface area (MM/GBSA) approach was used to calculate the binding-free energy (BFE). Flavonoids were selected based on their in vitro assays on SARS-CoV and SARS-CoV-2. Our pharmacokinetics study revealed that cyanidin showed good drug-likeness, fulfilled Lipinski's rule of five, and conferred favorable toxicity parameters. Furthermore, MD simulations showed that cyanidin interacts with spike protein and alters the conformation and binding-free energy suited. Finally, an in vitro assay indicated that about 50% reduction in the binding of hACE2 with S1-RBD in the presence of cyanidin-containing red grapes crude extract was achieved at approximately 1.25 mg/mL. Hence, cyanidin may be a promising adjuvant medication for the SARS-CoV-2 spike protein based on in silico and in vitro research. Hindawi 2022-11-09 /pmc/articles/PMC9668477/ /pubmed/36407836 http://dx.doi.org/10.1155/2022/3742318 Text en Copyright © 2022 Asmita Shrestha et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Shrestha, Asmita Marahatha, Rishab Basnet, Saroj Regmi, Bishnu P. Katuwal, Saurav Dahal, Salik Ram Sharma, Khaga Raj Adhikari, Achyut Chandra Basnyat, Ram Parajuli, Niranjan Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein |
title | Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein |
title_full | Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein |
title_fullStr | Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein |
title_full_unstemmed | Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein |
title_short | Molecular Docking and Dynamics Simulation of Several Flavonoids Predict Cyanidin as an Effective Drug Candidate against SARS-CoV-2 Spike Protein |
title_sort | molecular docking and dynamics simulation of several flavonoids predict cyanidin as an effective drug candidate against sars-cov-2 spike protein |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668477/ https://www.ncbi.nlm.nih.gov/pubmed/36407836 http://dx.doi.org/10.1155/2022/3742318 |
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