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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2023.1251529/full |
| _version_ | 1827806277655330816 |
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| author | Nusrat Shafiq Aiman Mehroze Warda Sarwar Uzma Arshad Shagufta Parveen Maryam Rashid Ariba Farooq Naila Rafiq Gezahign Fentahun Wondmie Yousef A. Bin Jardan Simone Brogi Mohammed Bourhia |
| author_facet | Nusrat Shafiq Aiman Mehroze Warda Sarwar Uzma Arshad Shagufta Parveen Maryam Rashid Ariba Farooq Naila Rafiq Gezahign Fentahun Wondmie Yousef A. Bin Jardan Simone Brogi Mohammed Bourhia |
| author_sort | Nusrat Shafiq |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T21:38:54Z |
| format | Article |
| id | doaj.art-94155ea9a8a8458398f85cb65c28f591 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-03-11T21:38:54Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-94155ea9a8a8458398f85cb65c28f5912023-09-26T13:53:15ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-09-011110.3389/fchem.2023.12515291251529Exploration of phenolic acid derivatives as inhibitors of SARS-CoV-2 main protease and receptor binding domain: potential candidates for anti-SARS-CoV-2 therapyNusrat Shafiq0Aiman Mehroze1Warda Sarwar2Uzma Arshad3Shagufta Parveen4Maryam Rashid5Ariba Farooq6Naila Rafiq7Gezahign Fentahun Wondmie8Yousef A. Bin Jardan9Simone Brogi10Mohammed Bourhia11Synthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, PakistanSynthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, PakistanSynthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, PakistanSynthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, PakistanSynthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, PakistanSynthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, PakistanDepartment of Chemistry, University of Lahore, Lahore, PakistanDepartment of Biochemistry, Government College Women University Faisalabad, Faisalabad, PakistanDepartment of Biology, Bahir Dar University, Bahir Dar, EthiopiaDepartment of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi ArabiaDepartment of Pharmacy, Pisa University, Pisa, ItalyDepartment of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, MoroccoSevere 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.https://www.frontiersin.org/articles/10.3389/fchem.2023.1251529/fullCOVID-19SARS-CoV-2phenolic acidsmolecular dockingdensity functional theory |
| spellingShingle | Nusrat Shafiq Aiman Mehroze Warda Sarwar Uzma Arshad Shagufta Parveen Maryam Rashid Ariba Farooq Naila Rafiq Gezahign Fentahun Wondmie Yousef A. Bin Jardan Simone Brogi Mohammed Bourhia 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 Frontiers in Chemistry COVID-19 SARS-CoV-2 phenolic acids molecular docking density functional theory |
| 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 | COVID-19 SARS-CoV-2 phenolic acids molecular docking density functional theory |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2023.1251529/full |
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