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Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy
Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins i...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562575/ https://www.ncbi.nlm.nih.gov/pubmed/37822772 http://dx.doi.org/10.3389/fchem.2023.1251529 |
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author | Shafiq, Nusrat Mehroze, Aiman Sarwar, Warda Arshad, Uzma Parveen, Shagufta Rashid, Maryam Farooq, Ariba Rafiq, Naila Wondmie, Gezahign Fentahun Bin Jardan, Yousef A. Brogi, Simone Bourhia, Mohammed |
author_facet | Shafiq, Nusrat Mehroze, Aiman Sarwar, Warda Arshad, Uzma Parveen, Shagufta Rashid, Maryam Farooq, Ariba Rafiq, Naila Wondmie, Gezahign Fentahun Bin Jardan, Yousef A. Brogi, Simone Bourhia, Mohammed |
author_sort | Shafiq, Nusrat |
collection | PubMed |
description | Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main protease (Mpro) and the receptor binding domain (RBD) using molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. To this end, thirty-five naturally occurring phenolics were identified and subjected to molecular docking simulation against the proteins. The results showed the compounds including rosmarinic acid, cynarine, and chlorogenic acid among many others possessed high binding affinities for both proteins as evident from their docking scores, with some possessing lower docking scores compared to the standard compound (Remdesivir). Further subjection of the hit compounds to drug-likeness, pharmacokinetics, and toxicity profiling revealed chlorogenic acid, rosmarinic acid, and chicoric acid as the compounds with desirable profiles and toxicity properties, while the study of their electronic properties via density functional theory calculations revealed rosmarinic acid as the most reactive and least stable among the sets of lead compounds that were identified in the study. Molecular dynamics simulation of the complexes formed after docking revealed the stability of the complexes. Ultimately, further experimental procedures are needed to validate the findings of this study. |
format | Online Article Text |
id | pubmed-10562575 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-105625752023-10-11 Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy Shafiq, Nusrat Mehroze, Aiman Sarwar, Warda Arshad, Uzma Parveen, Shagufta Rashid, Maryam Farooq, Ariba Rafiq, Naila Wondmie, Gezahign Fentahun Bin Jardan, Yousef A. Brogi, Simone Bourhia, Mohammed Front Chem Chemistry Severe acute respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) is the etiological virus of Coronavirus Disease 2019 (COVID-19) which has been a public health concern due to its high morbidity and high mortality. Hence, the search for drugs that incapacitate the virus via inhibition of vital proteins in its life cycle is ongoing due to the paucity of drugs in clinical use against the virus. Consequently, this study was aimed at evaluating the potentials of natural phenolics against the Main protease (Mpro) and the receptor binding domain (RBD) using molecular modeling techniques including molecular docking, molecular dynamics (MD) simulation, and density functional theory (DFT) calculations. To this end, thirty-five naturally occurring phenolics were identified and subjected to molecular docking simulation against the proteins. The results showed the compounds including rosmarinic acid, cynarine, and chlorogenic acid among many others possessed high binding affinities for both proteins as evident from their docking scores, with some possessing lower docking scores compared to the standard compound (Remdesivir). Further subjection of the hit compounds to drug-likeness, pharmacokinetics, and toxicity profiling revealed chlorogenic acid, rosmarinic acid, and chicoric acid as the compounds with desirable profiles and toxicity properties, while the study of their electronic properties via density functional theory calculations revealed rosmarinic acid as the most reactive and least stable among the sets of lead compounds that were identified in the study. Molecular dynamics simulation of the complexes formed after docking revealed the stability of the complexes. Ultimately, further experimental procedures are needed to validate the findings of this study. Frontiers Media S.A. 2023-09-26 /pmc/articles/PMC10562575/ /pubmed/37822772 http://dx.doi.org/10.3389/fchem.2023.1251529 Text en Copyright © 2023 Shafiq, Mehroze, Sarwar, Arshad, Parveen, Rashid, Farooq, Rafiq, Wondmie, Bin Jardan, Brogi and Bourhia. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Shafiq, Nusrat Mehroze, Aiman Sarwar, Warda Arshad, Uzma Parveen, Shagufta Rashid, Maryam Farooq, Ariba Rafiq, Naila Wondmie, Gezahign Fentahun Bin Jardan, Yousef A. Brogi, Simone Bourhia, Mohammed Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy |
title | Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy |
title_full | Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy |
title_fullStr | Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy |
title_full_unstemmed | Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy |
title_short | Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapy |
title_sort | exploration of phenolic acid derivatives as inhibitors of sars-cov-2 main protease and receptor binding domain: potential candidates for anti-sars-cov-2 therapy |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10562575/ https://www.ncbi.nlm.nih.gov/pubmed/37822772 http://dx.doi.org/10.3389/fchem.2023.1251529 |
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