[Home ] [Archive]   [ فارسی ]  
:: Main :: About :: Current Issue :: Archive :: Search :: Submit :: Contact ::
:: Volume 30, Issue 4 (10-2022) ::
Journal of Ilam University of Medical Sciences 2022, 30(4): 66-85 Back to browse issues page
Efficacy Evaluation of Quercetin and Its Analogues on the Main Protease Enzyme of the COVID-19 Using Molecular Docking Studies
Tooba Abdizadeh *
Clinical Biochemistry Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran , abdizadeh.t@skums.ac.ir
Abstract:   (384 Views)
Introduction: COVID-19 is an acute respiratory infectious disease caused by the SARS-CoV-2 virus. There is an urgent need to discover antiviral drugs for better performance against new strains of coronaviruses (CoVs) due to the rapid spread of the disease despite scientific advances in vaccine development. This study aimed to evaluate the efficacy of quercetin and its analogues on the COVID-19 Mpro enzyme.
Material & Methods: In this descriptive-analytical study, the three-dimensional structures of quercetin analogues (20 compounds), standard drugs (ritonavir and lopinavir), and the COVID-19 Mpro enzyme were obtained from PubChem and PDB databases for bioinformatics study, respectively. Molecular docking studies of the compounds on the
Mpro were performed using MOE-2014 software. Afterward, the physicochemical properties and biological activity of the compounds were predicted using Swiss ADME, PASS, and Swiss Target Prediction software.

Findings: The findings of the present study showed that the most important bonds involved in drug-receptor binding are hydrogen, hydrophobic, and π-π interaction bonds. The best docking results were obtained for Baicalein, Genistein, Naringenin, and Quercetin compounds with strong binding energy (-12.83 to -13.54 kcal/mol), compared to ritonavir and lopinavir. These compounds have a greater tendency to bind to the catalytic amino acids His41 and Cys145 and other key amino acids of the active site of the COVID-19 Mpro enzyme.
Discussion & Conclusion: Based on the results of bioinformatics studies, quercetin analogues had more effective inhibition than standard chemical drugs due to their suitable placement in the active site of the main protease enzyme of COVID-19 and can be good candidates for in vitro and in vivo studies.

Keywords: SARS-CoV-2, Flavonoid, Bioinformatics Studies, Physicochemical properties
Full-Text [PDF 1815 kb]   (172 Downloads)    
Type of Study: Research | Subject: Natural Resources
Received: 2022/04/3 | Accepted: 2022/05/16 | Published: 2022/10/7
1. Halim SA, Waqas M, Khan A, Al-Harrasi A. In silico prediction of novel inhibitors of SARS-CoV-2 main protease through structure-based virtual screening and molecular dynamic simulation. Pharmaceuticals 2021;14:896. doi.org/ 10.3390/ph14090896
2. Kase Y, Okano H. Neurological pathogenesis of SARS-CoV-2 (COVID-19): from virological features to clinical symptoms. Inflamm Regen 2021;41:1-7. doi.org/10.1186/s41232-021-00165-8
3. Rahbar-Karbasdehi E, Rahbar-Karbasdehi F. Clinical challenges of stress cardiomyopathy during coronavirus 2019 epidemic. Cell Mol Biomed Rep 2021;1: 88-90. doi.org/10.55705/cmbr.2021.145790.1018
4. Fazelinasab B. Biological Evaluation Of Coronaviruses And The Study Of Molecular Docking, Linalool, And Thymol As Orf1ab Protein Inhibitors And The Role Of Sars-Cov-2 Virus In Bioterrorism. J Ilam Uni Med Sci 2021;28:7796. doi.org/10.29252/sjimu.28.6.77
5. Guo Y-R, Cao Q-D, Hong Z-S, Tan Y-Y, Chen S-D, Jin H-J, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak–an update on the status. Mil Med Res 2020;7:1-10. doi.org/10.1186/s40779-020-00240-0
6. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 2020;579:270-73. doi.org/10.1038/s41586-020-2012-7
7. Arbour N, Day R, Newcombe J, Talbot PJ. Neuroinvasion by human respiratory coronaviruses. J Virol 2000;74:8913-21. doi.org/ 10.1128/JVI.74.19.8913-8921.2000
8. Van Der Hoek L, Pyrc K, Jebbink MF, Vermeulen-Oost W, Berkhout RJ, Wolthers KC, et al. Identification of a new human coronavirus. Nat Med 2004;10:368-73. doi.org/10.1038/nm1024
9. Yang D, Leibowitz JL. The structure and functions of coronavirus genomic 3′ and 5′ ends. Virus Res 2015;206:120-33. doi.org/10.1016/j.virusres.2015.02.025
10. Drosten C, Günther S, Preiser W, Van Der Werf S, Brodt H-R, Becker S, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med 2003; 348:1967-76. doi.org/10.1056/NEJMoa030747
11. Cui J, Li F, Shi Z-L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019;17:181-92. doi.org/10.1038/s41579-018-0118-9
12. Zaki AM, Van Boheemen S, Bestebroer TM, Osterhaus AD, Fouchier RA. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med 2012;367:1814-20. doi.org/10.1056/NEJMoa1211721
13. Yadav R, Chaudhary JK, Jain N, Chaudhary PK, Khanra S, Dhamija P, et al. Role of structural and non-structural proteins and therapeutic targets of SARS-CoV-2 for COVID-19. Cells 2021;10:821. doi.org/10.3390/cells10040821
14. Chen W, Wang Z, Wang Y, Li Y. Natural bioactive molecules as potential agents against SARS-CoV-2. Front Pharmacol 2021;12. doi.org/10.3389/ fphar.2021.702472
15. Kumar A, Choudhir G, Shukla SK, Sharma M, Tyagi P, Bhushan A, et al. Identification of phytochemical inhibitors against main protease of COVID-19 using molecular modeling approaches. J Biomol Struct Dyn 2021;39:3760-70. doi.org/10.1080/07391102.2020.1772112
16. Hussein R, Elkhair H. Molecular docking identification for the efficacy of some zinc complexes with chloroquine and hydroxy-chloroquine against main protease of COVID-19. J Mol Struct 2021;1231:129979. doi.org/10.1016/j.molstruc.2021.129979
17. Gyebi GA, Elfiky AA, Ogunyemi OM, Ibrahim IM, Adegunloye AP, Adebayo JO, et al. Structure-based virtual screening suggests inhibitors of 3-chymotrypsin-like protease of SARS-CoV-2 from Vernonia amygdalina and Occinum gratissimum. Comput Biol Med 2021;136:104671. doi.org/10.1016/j.compbiomed.2021.104671
18. Fontanet A, Autran B, Lina B, Kieny MP, Karim SSA, Sridhar D. SARS-CoV-2 variants and ending the COVID-19 pandemic. The Lancet 2021;397:952-54. doi.org/10.1016/S0140-6736 (21)00370-6
19. Volkan E. COVID-19: Structural considerations for virus pathogenesis, therapeutic strategies and vaccine design in the Novel SARS-CoV-2 Variants Era. Mol Biotechnol 2021;63:885-97. doi.org/10.1007/s12033-021-00353-4
20. Dai W, Zhang B, Jiang X-M, Su H, Li J, Zhao Y, et al. Structure-based design of antiviral drug candidates targeting the SARS-CoV-2 main protease. Science 2020;368:1331-5. doi.org/10.1126/science.abb4489
21. Zandi H, Harismah K. Computer-based tools for structural characterizations and activity specifications of natural products: a quick review. Lab-in-Silico 2021;2:50-54. doi.org/10.22034/ labinsilico21021050
22. Romano JD, Tatonetti NP. Informatics and computational methods in natural product drug discovery: a review and perspectives. Front Genet 2019;10:368. doi.org/10.3389/fgene.2019.00368
23. 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;10:171-86. doi.org/10.1007/s13659-020-00250-4
24. Pohl F, Kong Thoo Lin P. The potential use of plant natural products and plant extracts with antioxidant properties for the prevention/treatment of neurodegenerative diseases: in vitro, in vivo and clinical trials. Molecules 2018;23:3283. doi.org/10.3390/molecules23123283
25. Jo S, Kim S, Shin DH, Kim M-S. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhib Med Chem 2020;35:145-51. doi.org/10.1080/14756366.2019.1690480
26. Rupasinghe H. Special Issue “flavonoids and their disease prevention and treatment potential”: Recent advances and future perspectives. Molecules 2020;25:4746. doi.org/10.3390/ molecules 25204746
27. Alzaabi MM, Hamdy R, Ashmawy NS, Hamoda AM, Alkhayat F, Khademi NN, et al. Flavonoids are promising safe therapy against COVID-19. Phytochem Rev 2021:1-22. doi.org/10.1007/s11101-021-09759-z
28. Singh S, Sk MF, Sonawane A, Kar P, Sadhukhan S. Plant-derived natural polyphenols as potential antiviral drugs against SARS-CoV-2 via RNA‐dependent RNA polymerase (RdRp) inhibition: an in-silico analysis. J Biomol Struct Dyn 2021;39:6249-64. doi.org/10.1080/07391 102.2020.1796810
29. Tallei TE, Tumilaar SG, Niode NJ, Kepel BJ, Idroes R, Effendi Y, et al. Potential of plant bioactive compounds as SARS-CoV-2 main protease (Mpro) and spike (S) glycoprotein inhibitors: a molecular docking study. Scientifica 2020;2020. doi.org/10.1155/2020/6307457. eCo-llection 2020
30. Priyandoko D, Widowati W, Subangkit M, Jasaputra D, Wargasetia T, Sholihah I, et al. Molecular docking study of the potential relevance of the natural compounds isoflavone and myricetin to COVID-19. Int J Bioautomation 2021;25:271. doi.org/10.7546/ijba.2021.25.3.000796
31. Rehman MT, AlAjmi MF, Hussain A. Natural compounds as inhibitors of SARS-CoV-2 main protease (3CLpro): A molecular docking and simulation approach to combat COVID-19. Curr Pharm Des 2021;27:3577-89. doi.org/10.2174/1381612826999201116195851
32. Mouffouk C, Mouffouk S, Mouffouk S, Hambaba L, Haba H. Flavonols as potential antiviral drugs targeting SARS-CoV-2 proteases (3CLpro and PLpro), spike protein, RNA-dependent RNA polymerase (RdRp) and angiotensin-converting enzyme II receptor (ACE2). Eur J Pharmacol 2021;891:173759. doi.org/10.1016/j.ejphar.2020.173759
33. Alrasheid AA, Babiker MY, Awad TA. Evaluation of certain medicinal plants compounds as new potential inhibitors of novel corona virus (COVID-19) using molecular docking analysis. In Silico Pharmacol 2021;9:1-7. doi.org/10.1007/ s40203-020-00073-8
34. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 2000; 44: 235-49. doi.org/10.1016/s1056-8719(00)00107-6
35. Egan WJ, Merz KM, Baldwin JJ. Prediction of drug absorption using multivariate statistics. J Med Chem 2000;43:3867-77. doi.org/10. 1021/jm000292e
36. Goel RK, Singh D, Lagunin A, Poroikov V. PASS-assisted exploration of new therapeutic potential of natural products. Med Chem Res 2011;20:1509-14. doi.org/10.1007/s00044-010-9398-y
37. Muegge I, Heald SL, Brittelli D. Simple selection criteria for drug-like chemical matter. J Med Chem 2001;44:1841-46. doi.org/10.1021/ jm015507e
38. Arora S, Lohiya G, Moharir K, Shah S, Yende S. Identification of potential flavonoid inhibitors of the SARS-CoV-2 main protease 6YNQ: a molecular docking study. Digital Chin Med 2020;3:239-48. doi.org/10.1016/j.dcmed.2020.12.003
39. Owis AI, El-Hawary MS, El Amir D, Aly OM, Abdelmohsen UR, Kamel MS. Molecular docking reveals the potential of Salvadora persica flavonoids to inhibit COVID-19 virus main protease. RSC Adv 2020;10:19570-75. doi.org/10.1039/D0RA03582C
40. Cherrak SA, Merzouk H, Mokhtari-Soulimane N. Potential bioactive glycosylated flavonoids as SARS-CoV-2 main protease inhibitors: A molecular docking and simulation studies. PLoS One 2020;15:e0240653. doi.org/10.1371/ journal.pone.0240653
41. Das S, Sarmah S, Lyndem S, Singha Roy A. An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study. J Biomol Struct Dyn 2021;39:3347-57. doi.org/10.1080/07391102.2020.1763201
42. Omrani M, Bayati M, Mehrbod P, Bardazard KA, Nejad-Ebrahimi S. Natural products as inhibitors of COVID-19 main protease–A virtual screening by molecular docking. Pharm Sci 2021;27(Covid-19):S135-48. doi.org/10.34172/PS.2021.1
Send email to the article author

Add your comments about this article
Your username or Email:


Ethics code: IR.SKUMS.REC.1399.117

XML   Persian Abstract   Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Abdizadeh T. Efficacy Evaluation of Quercetin and Its Analogues on the Main Protease Enzyme of the COVID-19 Using Molecular Docking Studies. Journal title 2022; 30 (4) :66-85
URL: http://sjimu.medilam.ac.ir/article-1-7530-en.html

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 30, Issue 4 (10-2022) Back to browse issues page
مجله دانشگاه علوم پزشکی ایلام Journal of Ilam University of Medical Sciences
Persian site map - English site map - Created in 0.15 seconds with 31 queries by YEKTAWEB 4574