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

Document Type : Original Article

Authors

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.

Abstract

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.

Keywords

References

1. Jo S, Kim S, Shin DH, Kim MS. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med Chem. 2020 Dec;35(1):145-151. doi: 10.1080/14756366.2019.1690480. PMID: 31724441; PMCID: PMC6882434.
2. de Wilde AH, Snijder EJ, Kikkert M, van Hemert MJ. Host Factors in Coronavirus Replication. In: Tripp RA, Tompkins SM, editors. Roles of Host Gene and Non-coding RNA Expression in Virus Infection. Cham: Springer International Publishing; 2018. p. 1-42.
3. Arya R, Das A, Prashar V, Kumar M. Potential Inhibitors Against Papain-like Protease of Novel Coronavirus (COVID-19) from FDA Approved Drugs.s Preprint from ChemRxiv. doi: 10.26DOI: 10.26434/chemrxiv.11860011.v1 434/chemrxiv.11860011.v1.
4. Pillaiyar T, Manickam M, Namasivayam V, Hayashi Y, Jung SH. An Overview of Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy. J Med Chem. 2016 Jul 28;59(14):6595-628. doi: 10.1021/acs.jmedchem.5b01461. Epub 2016 Feb 29. PMID: 26878082; PMCID: PMC7075650.
5. Shah B, Modi P, Sagar SR. In silico studies on therapeutic agents for COVID-19: Drug repurposing approach. Life Sci. 2020 Jul 1;252:117652. doi: 10.1016/j.lfs.2020.117652. Epub 2020 Apr 9. PMID: 32278693; PMCID: PMC7194845.
6. Nabirotchkin S, Peluffo AE, Rinaudo P, Yu J, Hajj R, Cohen D. Next-generation drug repurposing using human genetics and network biology. Curr Opin Pharmacol. 2020 Apr;51:78-92. doi: 10.1016/j.coph.2019.12.004. Epub 2020 Jan 22. PMID: 31982325.
7. Tallei TE, Tumilaar SG, Niode NJ, Fatimawali F, Kepel BJ, Idroes R, et al. Potential of Plant Bioactive Compounds as SARS-CoV-2 Main Protease (Mpro) and Spike (S) Glycoprotein Inhibitors: A Molecular Docking Study. 2020.
8. Sabahi Z, Soltani F, Moein M. Insight into DNA protection ability of medicinal herbs and potential mechanisms in hydrogen peroxide damages model. Asian Pac J Trop Biomed. 2018;8:120-9
9. Lin SC, Ho CT, Chuo WH, Li S, Wang TT, Lin CC. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect Dis. 2017 Feb 13;17(1):144. doi: 10.1186/s12879-017-2253-8. PMID: 28193191; PMCID: PMC5307780.
10. Li H, Wu J, Zhang Z, Ma Y, Liao F, Zhang Y, Wu G. Forsythoside a inhibits the avian infectious bronchitis virus in cell culture. Phytother Res. 2011 Mar;25(3):338-42. doi: 10.1002/ptr.3260. PMID: 20677175; PMCID: PMC7168103.
11. Chen C, Zuckerman DM, Brantley S, Sharpe M, Childress K, Hoiczyk E, Pendleton AR. Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication. BMC Vet Res. 2014 Jan 16;10:24. doi: 10.1186/1746-6148-10-24. PMID: 24433341; PMCID: PMC3899428.
12. Annunziata G, Sanduzzi Zamparelli M, Santoro C, et al. May Polyphenols Have a Role Against Coronavirus Infection? An Overview of in vitro Evidence. Front Med (Lausanne). 2020;7:240. Published 2020 May 15. doi:10.3389/fmed.2020.00240
13. Weng J-R, Lin C-S, Lai H-C, Lin Y-P, Wang C-Y, Tsai Y-C, et al. Antiviral activity of Sambucus FormosanaNakai ethanol extract and related phenolic acid constituents against human coronavirus NL63. Virus Res. 2019;273:197767.
14. Stefaniu A, Pirvu L, Albu B, Pintilie L. Molecular Docking Study on Several Benzoic Acid Derivatives against SARS-CoV-2. Molecules. 2020 Dec 10;25(24):5828. doi: 10.3390/molecules25245828. PMID: 33321862; PMCID: PMC7770597.
15. Sujit Kumar, M.; Rajguru Rajesh Raman, M.; Saumya, D.; Jogeswar, P., Identification of Putative Plant Based Antiviral Compounds to Fight Against SARS-CoV-2 Infection. 2020.
16. Orhan IE, Senol Deniz FS. Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2? Nat Prod Bioprospect. 2020 Aug;10(4):171-186. doi: 10.1007/s13659-020-00250-4. Epub 2020 Jun 11. PMID: 32529545; PMCID: PMC7289229.
17. Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph. 1996 Feb;14(1):33-8, 27-8. doi: 10.1016/0263-7855(96)00018-5. PMID: 8744570.
18. Fereidoonnezhad M, Faghih Z, Mojaddami A, Sakhteman A, Rezaei Z. A comparative docking studies of dichloroacetate analogues on four isozymes of pyruvate dehydrogenase kinase in humans. dent. 2016;1(4):5.
19. Jin Z, Du X, Xu Y, Deng Y, Liu M, Zhao Y, et al. Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors. Nature. 2020 Jun;582(7811):289-293. doi: 10.1038/s41586-020-2223-y. Epub 2020 Apr 9. PMID: 32272481.
20. Sabet R, Khabnadideh S, Fathi D, Emami L. QSAR and Docking Study of Isatin Analogues as Cytotoxic Agents. Journal of Pharmaceutical Research International. 2019;27:1-22.
21. Sabet R, Jafroudi I. QSAR, Docking Study of Isatin Analogues as Anti-bacterial Agents for Design New Compounds. Journal of Pharmaceutical Research International. 2019;31(5):1-24.
22. Emami L, Sabet R, Sakhteman A, Zade MK. Quantitative Structure–Activity Relationship and Molecular Docking Studies of Imidazolopyrimidine Amides as Potent Dipeptidyl Peptidase-4 (DPP4) Inhibitors. Journal of Pharmaceutical Research International. 2019;27(6):1-15.
23. Chen CN, Lin CP, Huang KK, et al. Inhibition of SARS-CoV 3C-like Protease Activity by Theaflavin-3,3'-digallate (TF3). Evid Based Complement Alternat Med. 2005;2(2):209-215. doi:10.1093/ecam/neh081.
24. Yi L, Li Z, Yuan K, Qu X, Chen J, Wang G, et al. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J Virol. 2004 Oct;78(20):11334-9. doi: 10.1128/JVI.78.20.11334-11339.2004. PMID: 15452254; PMCID: PMC521800.
25. Chen L, Li J, Luo C, Liu H, Xu W, Chen G, et al. Binding interaction of quercetin-3-beta-galactoside and its synthetic derivatives with SARS-CoV 3CL(pro): structure-activity relationship studies reveal salient pharmacophore features. Bioorg Med Chem. 2006 Dec 15;14(24):8295-306. doi: 10.1016/j.bmc.2006.09.014. Epub 2006 Oct 12. PMID: 17046271; PMCID: PMC7125754.
26. Ryu YB, Jeong HJ, Kim JH, Kim YM, Park JY, Kim D, et al. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CL(pro) inhibition. Bioorg Med Chem. 2010 Nov 15;18(22):7940-7. doi: 10.1016/j.bmc.2010.09.035. Epub 2010 Sep 19. PMID: 20934345; PMCID: PMC7126309.
Trends in Pharmaceutical Sciences
Volume 7, Issue 2
June 2021
Pages 117-126

Files

Share

How to cite

Statistics