Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2

Heba I Ghamry; Amany Belal; Mohamed Kandeel El-Ashrey; Haytham O Tawfik; Reem I Alsantali; Ahmad J Obaidullah; Ahmed A El-Mansi; Doaa Abdelrahman

doi:10.1038/s41598-023-34189-6

Evaluating the ability of some natural phenolic acids to target the main protease and AAK1 in SARS COV-2

Sci Rep. 2023 May 5;13(1):7357. doi: 10.1038/s41598-023-34189-6.

Authors

Heba I Ghamry¹, Amany Belal², Mohamed Kandeel El-Ashrey^{3

4}, Haytham O Tawfik⁵, Reem I Alsantali⁶, Ahmad J Obaidullah⁷, Ahmed A El-Mansi^{8

9}, Doaa Abdelrahman¹⁰

Affiliations

¹ Nutrition and Food Sciences, Department of Home Economics, College of Home Economics, King Khalid University, P.O. Box 960, Abha, 61421, Saudi Arabia.
² Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia. a.belal@tu.edu.sa.
³ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini St., Cairo, 11562, Egypt.
⁴ Medicinal Chemistry Department, Faculty of Pharmacy, King Salman International University, Ras-Sedr, South Sinai, Egypt.
⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, 31527, Egypt.
⁶ Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, P.O. Box 11099, Taif, 21944, Saudi Arabia.
⁷ Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
⁸ Biology Department, Faculty of Science, King Khalid University, Abha, Saudi Arabia.
⁹ Zoology Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
¹⁰ Department of Clinical Sciences, College of Medicine, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Abstract

Researchers are constantly searching for drugs to combat the coronavirus pandemic caused by SARS-CoV-2, which has lasted for over two years. Natural compounds such as phenolic acids are being tested against Mpro and AAK1, which are key players in the SARS-CoV-2 life cycle. This research work aims to study the ability of a panel of natural phenolic acids to inhibit the virus's multiplication directly through Mpro and indirectly by affecting the adaptor-associated protein kinase-1 (AAK1). Pharmacophore mapping, molecular docking, and dynamic studies were conducted over 50 ns and 100 ns on a panel of 39 natural phenolic acids. Rosmarinic acid (16) on the Mpro receptor (- 16.33 kcal/mol) and tannic acid (17) on the AAK1 receptor (- 17.15 kcal/mol) exhibited the best docking energy against both receptors. These favourable docking score values were found to be superior to those of the co-crystallized ligands. Preclinical and clinical research is required before using them simultaneously to halt the COVID-19 life cycle in a synergistic manner.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing
COVID-19*
Coronavirus 3C Proteases*
Humans
Molecular Docking Simulation
Molecular Dynamics Simulation
Oligonucleotides
Protease Inhibitors*
SARS-CoV-2

Substances

AAK1 protein, human
Adaptor Proteins, Signal Transducing
Oligonucleotides
phenolic acid
Protease Inhibitors
3C-like proteinase, SARS-CoV-2
Coronavirus 3C Proteases