Comparison of COVID-19 Virus Main Protease Inhibition Activities of Phenolic Acids By Molecular Docking

Document Type : Original Article


1 Department of Medicinal Chemistry, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Medical Biochemistry, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

3 Pharmaceutical Sciences Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

4 Medicinal Plants Processing Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.


The Covid-19 pandemic is new challenge all around the world. This pandemic provides an emergency development of vaccines and drugs against this virus. As main proteases of CoV-19 have essential roles in the transmission and virulence of the virus.  So, this enzyme has been considered as a critical target to inhibit COVID-19. Natural compounds are well known as rich sources of antiviral drugs due to their structural diversity and safety. In this study, we have screened thirteen phenolic acids (Cinnamic acid and Hydroxy benzoic derivatives) to compare the potential inhibitory activity of these molecules against COVID-19 protease. Systematic molecular docking simulation was done using AutoDock 4.2.6 to achieve the binding affinities and interactions between phenolic acids and protease. Cinnamic acids are better protease inhibitors in comparison with benzoic acid derivatives. Among Cinnamic acid derivatives, Rosmarinic acid exhibited the minimum Gibbs binding energy and highest docking scores. Also, Chorgenic > Ellagic > Ferulic acid could more effective respectively . According to obtained results, Rosmarinic acid has formed strong hydrogen bonding interaction with His163A, Ser144A, Cys145A, Gly143A and Thr26A, while the propyl cyclohexadione of Rosmarinic acid formed hydrophobic interaction with residue Gly 143A. It seems that Cinnamic acid derivatives of phenolic acid, particularly Rosmarinic acid could be efficient SARS-CoV 3CLpro inhibitors. In the next step, it is necessary to survey the effect of these natural products in inhibition of SARS-CoV replication through cell culture and in vitro assays. This study will improve preclinical knowledge about potential of natural compounds as SARS-CoV inhibitors.


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