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

Chemistry

Naila Rafiq¹  Gezahign Fentahun Wondmie²  Mohammed Bourhia³  Ariba Farooq⁴  Yousef A. Bin Jardan⁵  Simone Brogi⁶  Aiman Mehroze⁷  Warda Sarwar⁷  Shagufta Parveen⁷  Uzma Arshad⁷  Nusrat Shafiq⁷  Maryam Rashid⁷ 

[1]Department of Biochemistry, Government College Women University Faisalabad, Faisalabad, Pakistan

[2]Department of Biology, Bahir Dar University, Bahir Dar, Ethiopia

[3]Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune, Morocco

[4]Department of Chemistry, University of Lahore, Lahore, Pakistan

[5]Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia

[6]Department of Pharmacy, Pisa University, Pisa, Italy

[7]Synthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad, Faisalabad, Pakistan

关键词: COVID-19;    SARS-CoV-2;    phenolic acids;    molecular docking;    density functional theory;   

DOI  :  10.3389/fchem.2023.1251529

 received in 2023-07-01, accepted in 2023-09-06,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

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Copyright © 2023 Shafiq, Mehroze, Sarwar, Arshad, Parveen, Rashid, Farooq, Rafiq, Wondmie, Bin Jardan, Brogi and Bourhia.