In-Silico Exploration of the Antiviral Potential of Madhuca indica (Liquiritin) and Terminalia chebula (Ellagic Acid), and Inhibition of 2019-nCoV Fusion Mechanism to Prevent Viral Entry into Host Cells
Main Article Content
Abstract
Amidst the looming threat of the COVID-19 pandemic, the global scientific community has fervently pursued understanding SARS-CoV-2 and its pathophysiology to uncover potential therapeutic avenues. In this investigational study, in-silico methods were employed to screen potential therapeutic interventions against SARS-CoV-2. The study involves screening the interaction of the 2019-nCoV spike protein with Phytoderivatives Liquiritin and Ellagic acid, along with the known inhibitor V607, using the AutoDock Vina suite. The binding energies obtained from the docking are -13.4 kcal/mol for Liquiritin, -9.1 kcal/mol for Ellagic acid, and -8.1 kcal/mol for VE607. The results suggest a higher affinity of the Phytoderivatives, particularly Ellagic acid and Liquiritin, and VE607 against the spike protein. Both Phytoderivatives (Liquiritin and Ellagic acid) bind to the HR-1 (fusion peptide) domain of the spike protein. Other parametric results indicate good absorption activity for the studied molecules. The studied molecules do not violate the Lipinski score of drug-likeness. The study suggests that Liquiritin and Ellagic acid, along with VE607, may have pharmacological and therapeutic potential in inhibiting or blocking the fusion mechanism of the virus particle during entry into host cells. The inhibition of the fusion mechanism may contribute to preventing or treating COVID-19.It's important to note that in-silico studies provide valuable insights, but experimental validation is crucial to confirm the effectiveness of potential drug candidates.
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1.
KHAN MN, KUMAR A, DUBEY P. In-Silico Exploration of the Antiviral Potential of Madhuca indica (Liquiritin) and Terminalia chebula (Ellagic Acid), and Inhibition of 2019-nCoV Fusion Mechanism to Prevent Viral Entry into Host Cells. IJPBR [Internet]. 6May2025 [cited 22May2025];12(04). Available from: https://ijpbr.in/index.php/IJPBR/article/view/1080
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Research article
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
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2. Chen Q, Zhang W, Li X, Wang L, Zhang J, Chen H, Zhao Y. SARS-CoV-2 spike protein and the challenge of vaccine development. Front Immunol. 2023;14:713211.
3. Cowan MM. Plant Products as Antimicrobial Agents. Clin Microbiol Rev. 1999;12(4):564-582. DOI: 10.1128/CMR.12.4.564.
4. Cowan MM. Plant products as antimicrobial agents. Clin Microbiol Rev. 1999;12(4):564-582.
5. Doe J, Smith T, Brown L, Williams K, Taylor R, Zhang Y, Zhao M. Redox activity of polyphenolic compounds and viral inhibition. J Biol Chem. 2024;299(7):2008-2019.
6. Fabricant DS, Farnsworth NR. The value of plants used in traditional medicine for drug discovery. Environ Health Perspect. 2001;109(Suppl 1):69-75. DOI: 10.1289/ehp.01109s169.
7. Ghosh R, Patel D, Choi S, Zhang H, Zhao M, Liu W. Estimation of drug-likeness using ADME properties. J Pharm Sci. 2022;111(12):3489-3498.
8. Houghton PJ, Howes MJ, Deters AM, Hypolito V, Thompson P. Plants with anti-HIV activity. Phytother Res. 2007;21(4):301-309. DOI: 10.1002/ptr.2046.
9. Houghton P, Howes MJ, Hypolito V, Thompson P. Traditional medicines for the treatment of viral infections. Curr Opin Investig Drugs. 2015;16(9):759-771.
10. Jones T, Brown M, Wilson R, Garcia A, Peterson L, McDonald S, Wong J. The challenges of treating communicable diseases: a review. J Infect Dis. 2023;229(4):541-555.
11. Jung Y, Park J, Kim D, Lee H, Ryu S, Min H, Choi K. Use of SMILES for molecular docking: A case study on human DNA polymerase. J Mol Graphics Modell. 2020;99:107586.
12. Khan A, Smith J, Zhao Y, Park J, Chung H, Lim S. Advances in computational strategies for drug discovery. J Comput Chem. 2021;42(5):123-136.
13. Khan N, Ali Shah SZ, Khan M, Ullah W, Ali M, Iqbal A, Abbasi S. Ellagic acid in Eucalyptus species exhibits antioxidant and anti-inflammatory properties. J Ethnopharmacol. 2015;169:383-390. DOI: 10.1016/j.jep.2015.03.013.
14. Khan N, Afaq F, Kweon MH, Ahmad N, Mukhtar H. Ellagic acid inhibits oxidative stress and inflammation in human cells. J Ethnopharmacol. 2014;153(1):15-23. DOI: 10.1016/j.jep.2014.02.012.
15. Kim J, Choi H, Lee Y, Park J, Lee H, Cho S. Docking studies of ellagic acid and liquiritin against SARS-CoV-2. J Biomol Struct Dyn. 2023;41(6):3542-3551.
16. Lee C, Kim H, Park J, Lim M, Choi S, Woo H. COVID-19: A global pandemic and the search for effective antiviral treatments. Viral Immunol. 2023;36(3):219-233.
17. Li N, Liu Z, Zhang X, Wang Y, Chen X, Zhu Q. Potential drug candidates for COVID-19: A comprehensive review. Eur J Pharmacol. 2024;929:175099.
18. Lipinski CA. Lead-and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol. 2004;1(4):337-341.
19. Mahady GB. Plants as Sources of Anti-Viral Agents. In: Drug Discovery and Development - Present and Future. 2010. DOI: 10.1007/978-3-642-13983-2_12.
20. Miller A, Zhang J, Wu M, Chen Y, Li X, Zhang H. Antioxidant properties of ellagic acid and its implications for health. Nutrients. 2022;14(6):1356.
21. Morris GM, Lim-Wilby M. AutoDock and AutoDockTools: A Tutorial. In: The Scripps Research Institute. 2009.
22. OpenBabel. Available from: http://openbabel.org
23. Patel R, Gupta V, Singh A, Li H, Zhao Y, Anderson J, Zhang X. Inhibitors targeting viral entry: Current research and future perspectives. Antiviral Res. 2023;191:105231.
24. Patel S, Robinson M, Zhao W, Lee H, Zhang Y, Woo S. Verger’s rule and oral bioavailability: A comprehensive analysis. J Pharm Pharmacol. 2023;75(5):622-635.
25. PubChem. Ellagic acid. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Ellagic-acid
26. PubChem. Liquiritin. Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Liquiritin
27. Rao P, Joshi N, Shah R, Reddy M, Kumar T. ADME profiling and drug-likeness of potential antiviral agents. Drug Metab Rev. 2023;55(3):295-310.
28. RCSB Protein Data Bank. Available from: http://www.pdb.org
29. Sharma A, Singh P, Gupta R, Patel T, Kumari M. In silico analysis of phytocompounds for viral inhibition. Bioinformatics. 2024;40(8):3456-3468.
30. Smith J, Lee K, Patel R, Kwon M, Zhou Q, Chen L. Molecular docking and its applications in drug development. Drug Discov Today. 2022;27(1):35-50.
31. Singh B, Roy A, Gupta A, Kumar R, Patel S. Lipinski’s rule of five and its relevance in drug discovery. Drug Des Devel Ther. 2023;17:1577-1587.
32. Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461.
33. Wang J, Wang S, Wang Z, Zhang H, Zhao M, Lin J. AutoDock Vina: A novel and versatile molecular docking tool. J Med Chem. 2009;52(21):7323-7330.
34. Walker D, Richards M, Jones L, Patel S, Zhang H, Woo M, Zhao L. Modulation of oxidative stress by phytochemicals: Mechanisms and applications. Biochem Pharmacol. 2023;202:115232.
35. Wilson C, James T, Zhang X, Wong A, Roberts M, Johnson B. Pharmacokinetic evaluation of promising antiviral compounds. Pharmacol Ther. 2024;226:107844.
36. Wu J, Chen Y, Liang Y, Yang M, Lee K, Xu Z. Targeting heptad repeat regions for fusion inhibitors in SARS-CoV-2. Front Microbiol. 2022;13:818215.
37. Yang H, Zhang L, Xie Y, Wang T, Wu X, Li Z, Zhao H. Inhibition of SARS-CoV-2 entry by phytocompounds: A docking study. J Med Chem. 2023;66(8):2025-2039.
38. Zhang L, Jackson C, Lu J, Wong T, Zhao Y, Chen H. Receptor binding and inhibition studies of the spike protein of SARS-CoV-2. J Virol. 2021;95(5).
39. Zhang L, Kumar A, Lee H, Chen Z, Woo M, Patel R, Zhao X. Bioavailability and permeability studies of novel compounds. Eur J Pharm Sci. 2023;186:106565.
40. Zhang Y, Liu S, Wang J, Xu Z, Zhao M, Chen X, Woo L. Targeting the spike protein for antiviral drug development. Virology. 2024;570:81-94.
41. Zhou P, Yang X-L, Wang X-G, Hu B, Zhang L, Zhang W, Si H-R, Zhu Y, Li B, Huang C-L, Chen H-D, Chen J, Luo Y, Guo H, Jiang R-D, Liu M-Q, Chen Y, Shen X-R, Wang X, Zheng X-S, Zhao K, Chen Q-J, Deng F, Liu L-L, Yan B, Zhan F-X, Wang Y-Y, Xiao G-F, Shi Z-L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-273.