NATURAL COMPOUNDS FROM DJIBOUTIAN MEDICINAL PLANTS AS INHIBITORS OF COVID-19 BY IN SILICO INVESTIGATIONS

  • ABDIRAHMAN ELMI Medicinal Research Institute, Centre d’Etudes et de Recherche de Djibouti, IRM-CERD, Route de l’Aéroport, Djibouti
  • S. AL-JAWAD SAYEM International Islamic University Chittagong, Departement of Pharmacy, Bangladesh
  • MOHAMED AHMED Medicinal Research Institute, Centre d’Etudes et de Recherche de Djibouti, IRM-CERD, Route de l’Aéroport, Djibouti
  • FATOUMA ABDOUL-LATIF Medicinal Research Institute, Centre d’Etudes et de Recherche de Djibouti, IRM-CERD, Route de l’Aéroport, Djibouti

Abstract

Objective: The new coronavirus type SARS-Cov 2 (severe acute respiratory syndrome), which appeared in autumn 2019 in China, became a global pandemic in a few months. In this work, we looked for the potential anti SARS-Cov 2 of the compounds isolated from three Djiboutian medicinal plants, namely Acacia seyal, Cymbopogon commutatus, and Indigofera caerulea.


Methods: We carried out a molecular docking with nine biomolecules, β-Sitosterol, Quercetin, Catechin, Lupeol, Rutin, Kaempferol, Gallic acid, Piperitone and Limonene on three target sites which are SARS-CoV-2 main protease (Mp), SARS-CoV-2 receptor-binding domain (RBD) and human furin protease. These targets are chosen because of their role in the process of penetration of the virus into human cells and its multiplication. Moreover, the predictions of pharmacokinetic parameters as well as toxicological properties have been determined using an online bioinformatics tool named SwissADME and AdmetSAR respectively.


Results: The phenolic compounds have a very good affinity on these three target sites with binding energies of up to-9.098 kcal/mol for rutin on SARS-CoV-2 Mp, much better than the two reference drugs hydroxychloroquine (-5.816 kcal/mol) and remdesivir (-7.194 kcal/mol). Except for β-Sitosterol, the tested biomolecules have weak toxicity.


Conclusion: These natural compounds can be used against covid 19 pending In vitro and In vivo evaluations.

Keywords: Biomolecules, Djibouti medicinal plant, Anticovid 19 and molecular docking

References

1. Vabret A, Dina J, Brison E, Brouard J, Freymuth F. Coronavirus humains (HCoV). Pathol Biol 2009;57:149–60.
2. INSERM Lancement d’un essai clinique européen contre le Covid-19. Available from: https://presse.inserm.fr/lancement-dun-essai-clinique-europeen-contre-le-covid-19/38737 [Last accessed on 06 May 2020]
3. Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell 2020;181:281-92.
4. Dhama K, Sharun K, Tiwari R, Dadar M, Malik YS, Singh KP, et al. COVID-19, an emerging coronavirus infection: advances and prospects in designing and developing vaccines, immunotherapeutics, and therapeutics. Human Vaccines Immunother 2020;1–7. Doi:10.1080/21645515.2020.1735227.
5. Ajibesin KK, Ekpo BA, Bala DN, Essien EE, Adesanya SA. Ethnobotanical survey of Akwa Ibom state of Nigeria. J Ethnopharmacol 2008;115:387–408.
6. Mahmoud Ayan, Nour Ayeh M, Saad O, Camberlin P, Gemenne F, De longueville F, et al. Importance des récentes variations pluviométriques a djibouti et besoins de quantification de leurs impacts. In: Proceedings of the colloques et congrès scientifiques: Communication poster, Djibouti; 2014.
7. Elmi A, Spina R, Abdoul Latif F, Yagi S, Fontanay S, Risler A, et al. Rapid screening for bioactive natural compounds in Indigofera caerulea Rox fruits. Ind Crops Prod 2018;125:123–30.
8. Elmi A, Spina R, Risler A, Philippot S, Merito A, Duval RE, et al. Evaluation of antioxidant and antibacterial activities, cytotoxicity of acacia seyal del bark extracts and isolated compounds. Molecules 2020;25:2392.
9. Elmi A. Etudes phytochimiques de plantes médicinales djiboutiennes a effets antimicrobiens et anticancereux. These Nancy; 2018.
10. Fearon D, Powell A, Douangamath A, Owen C. PanDDA analysis of COVID-19 main protease against the DSI-poised Fragment Library. Available from: http://www.rcsb.org/structure/5R84 [Last accessed on 07 May 2020].
11. Dahms SO, Jiao GS, Than ME. Structural studies revealed active site distortions of human furin by a small molecule inhibitor. ACS Chem Biol 2017;12:1211–6.
12. Shang J, Ye G, Shi K, Wan Y, Luo C, Aihara H, et al. Structural basis of receptor recognition by SARS-CoV-2. Nature 2020;581:221-4.
13. Berman HM, Battistuz T, Bhat TN, Bluhm WF, Bourne PE, Burkhardt K, et al. The protein data bank. Acta Crystallogr D Biol Crystallogr 2002;58:899–907.
14. Friesner RA, Banks JL, Murphy RB, Halgren TA, Klicic JJ, Mainz DT, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 2004;47:1739–49.
15. Borrel A, Regad L, Xhaard H, Petitjean M, Camproux AC. PockDrug: a model for predicting pocket druggability that overcomes pocket estimation uncertainties. J Chem Inf Model 2015;55:882–95.
16. Discovery studio life science modeling and simulations; 2008.
17. Daina A, Michielin O, Zoete V. Swiss ADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:42717. Doi:10.1038/srep42717.
18. Minovski N, Perdih A, Solmajer T. Combinatorially-generated library of 6-fluoroquinolone analogs as potential novel antitubercular agents: a chemometric and molecular modeling assessment. J Mol Model 2012;18:1735–53.
19. Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, et al. admet SAR: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 2012;52:3099–105.
20. Rane JS, Chatterjee A, Kumar A, Ray S. Targeting SARS-CoV-2 spike protein of covid-19 with naturally occurring phytochemicals: an in silco study for drug development; 2020.
21. Nguyen TTH, Woo HJ, Kang HK, Nguyen VD, Kim YM, Kim DW, et al. Flavonoid-mediated inhibition of SARS coronavirus 3C-like protease expressed in Pichia pastoris. Biotechnol Lett 2012;34:831–8.
22. Park JY, Yuk HJ, Ryu HW, Lim SH, Kim KS, Park KH, et al. Evaluation of polyphenols from Broussonetia papyrifera as coronavirus protease inhibitors. J Enzyme Inhibition Med Chem 2017;32:504–12.
23. Khaerunnisa S, Kurniawan H, Awaluddin R, Suhartati S, Soetjipto S. Potential inhibitor of covid-19 main protease (Mpr°) from several medicinal plant compounds by molecular docking study. Med Pharmacol 2020. Doi:10.20944/preprints 202003.0226.v1
24. Jo S, Kim S, Shin DH, Kim MS. Inhibition of SARS-CoV 3CL protease by flavonoids. J Enzyme Inhibition Med Chem 2020;35:145–51.
25. Sharma R, Panigrahi P, Suresh CG. In silico analysis of binding site features and substrate selectivity in plant flavonoid-3-O glycosyltransferases (F3GT) through molecular modeling, docking and dynamics simulation studies. PLoS One 2014;9:e92636.
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ELMI, A., S. A.-J. SAYEM, M. AHMED, and F. ABDOUL-LATIF. “NATURAL COMPOUNDS FROM DJIBOUTIAN MEDICINAL PLANTS AS INHIBITORS OF COVID-19 BY IN SILICO INVESTIGATIONS”. International Journal of Current Pharmaceutical Research, Vol. 12, no. 4, July 2020, pp. 52-57, doi:10.22159/ijcpr.2020v12i4.39051.
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