MOLECULAR DOCKING STUDY BETWEEN 3 THAI MEDICINAL PLANTS COMPOUNDS AND COVID-19 THERAPEUTIC PROTEIN TARGETS: SARS-COV-2 MAIN PROTEASE, ACE-2, AND PAK-1
DOI:
https://doi.org/10.22159/ijap.2021.v13s2.08Keywords:
Thai Medicinal plants, Mpro, ACE-2, PAK-1, COVID-19, SARS-CoV-2Abstract
Objective: The present study aimed to evaluate those 3 compounds among 122 Thai natural products by using a molecular docking approach to inhibit Main Protease (Mpro) of SARS-CoV-2 (PDB code: 6Y2F), Angiotensin Converting Enzyme (ACE)-2 (PDB code: 1R4L), and PAK-1 kinase (PDB code: 5DEW).
Methods: The evaluation was performed on the docking scores calculated using AutoDock Vina as a docking engine and interaction profile analysis through 2-dimensional visualization using LigPlot+. The determination of the docking score was done by selecting the conformation of the ligand that has the lowest binding free energy (best pose).
Result: The results of this study indicate that overall, Panduratin A has the best affinity in inhibiting the main protease of SARS-CoV-2, ACE-2, and PAK-1 compared to other compounds.
Conclusion: The three thai medicinal plants compound has the potential to be developed as specific therapeutic agents against COVID-19.
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References
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2. Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E. A novel coronavirus emerging in China-key questions for impact assessment. N England J Med 2020;382:692-4.
3. Malik YS, Kumar N, Sircar S, Kaushik R, Bhat S, Dhama K, et al. Coronavirus disease pandemic (COVID-19): challenges and a global perspective. Pathogens 2020;9:519.
4. Bansal M, Walia MK. The covid 19-an overview on epidemiology, symptoms, prevention, management, treatment and role of health workers. Int J Appl Pharm 2020;12:36-41.
5. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269-71.
6. Lim J, Jeon S, Shin HY, Kim MJ, Seong YM, Lee WJ, et al. Case of the index patient who caused tertiary transmission of COVID-19 infection in Korea: the application of lopinavir/ritonavir for the treatment of COVID-19 infected pneumonia monitored by quantitative RT-PCR. J Korean Med Sci 2020;35:1-6.
7. Diyy A ASM, Thomas NV. Potential therapeutic avenues for COVID-19 therapy. Int J Pharm Pharm Sci 2020;12:11-4.
8. Anand K, Ziebuhr J, Wadhwani P, Mesters JR, Hilgenfeld R. Coronavirus main proteinase (3CLpro) structure: basis for design of anti-SARS drugs. Science 2003;300:1763-7.
9. Chen YW, Yiu CP, Wong KY. Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like protease (3CL pro) structure: virtual screening reveals velpatasvir, ledipasvir, and other drug repurposing candidates. F1000 Res 2020;9:1-17.
10. Zhang L, Lin D, Sun X, Curth U, Drosten C, Sauerhering L, et al. Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved ?-ketoamide inhibitors. Science 2020;368:409-12.
11. Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science 2020;367:1444-8.
12. Towler P, Staker B, Prasad SG, Menon S, Tang J, Parsons T, et al. ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis. J Biol Chem 2004;279:17996-8007.
13. Maruta H. Herbal therapeutics that block the oncogenic kinase PAK1:a practical approach towards PAK1?dependent diseases and longevity. Phytother Res 2014;28:656-72.
14. Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J 2005;2:1-10.
15. Lu S, Strand KA, Mutryn MF, Tucker RM, Jolly AJ, Furgeson SB, et al. PTEN (Phosphatase and Tensin Homolog) Protects Against Ang II (Angiotensin II)-induced pathological vascular fibrosis and remodeling—brief report. Arterioscler Thromb Vasc Biol 2020;40:394-403.
16. Chen IY, Chang SC, Wu HY, Yu TC, Wei WC, Lin S, et al. Upregulation of the chemokine (CC motif) ligand 2 via a severe acute respiratory syndrome coronavirus spike-ACE2 signaling pathway. J Virol 2010;84:7703-12.
17. Kanjanasirirat P, Suksatu A, Manopwisedjaroen S, Munyoo B, Tuchinda P, Jearawuttanakul K, et al. High-content screening of thai medicinal plants reveals boesenbergia rotunda extract and its component panduratin a as anti-SARS-CoV-2 agents. Researchsquare 2020;10:1-22.
18. Cole JC, Murray CW, Nissink JW, Taylor RD, Taylor R. Comparing protein–ligand docking programs is difficult. Prot Struct Func Bioinf 2005;60:325-32.
19. 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;31:455-61.
20. Wallace AC, Laskowski RA, Thornton JM. LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions. Protein Eng Des Sel 1995;8:127-34.
21. Flamandita D, Lischer K, Pratami DK, Aditama R, Sahlan M. Molecular docking analysis of podophyllotoxin derivatives in sulawesi propolis as potent inhibitors of protein kinases. AIP Conf Proc 2020;2230:020010.
22. Hsu MF, Kuo CJ, Chang KT, Chang HC, Chou CC, Ko TP, et al. Mechanism of the maturation process of SARS-CoV 3CL protease. J Biol Chem 2005;280:31257-66.
Published
10-02-2021
How to Cite
ASIH, S. C., IRDIANI, R., SAHLAN, M., & NASIKIN, M. (2021). MOLECULAR DOCKING STUDY BETWEEN 3 THAI MEDICINAL PLANTS COMPOUNDS AND COVID-19 THERAPEUTIC PROTEIN TARGETS: SARS-COV-2 MAIN PROTEASE, ACE-2, AND PAK-1. International Journal of Applied Pharmaceutics, 13(2), 41–48. https://doi.org/10.22159/ijap.2021.v13s2.08
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