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Pertanika Journal of Science & Technology

Official journal of Universiti Putra Malaysia for scholarly work across science, engineering and related technologies.

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Research article

In Silico Screening of Breadfruit (Artocarpus altilis) Prenylated Flavonoids Identify Potential SARS-CoV Inhibitors

Nisha Govender, Siti Nur Athirah Mohd Kaspi, Thennavan Krishnan and Zeti-Azura Mohamed-Hussein

Volume 31, Issue 5 August 2023 Published 31 July 2023
https://doi.org/10.47836/pjst.31.5.01
KeywordsArtocarpus altilis, COVID-19, dietary plant, herbal medicine, molecular docking, prenylated flavonoids, SARS-CoV-2, traditional medicine
Article content

Abstract

Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health threat. Traditional herbals and dietary plants with medicinal values have a long antiviral history and, thus, are extensively studied in COVID-19 therapeutics development. Breadfruit (Artocarpus altilis) is a food crop with rich nutrient composition. This study screened selected breadfruit prenylated flavonoids for their potential inhibitory activities against the SARS-CoV family receptors using molecular docking and molecular dynamics (MD) simulation. The A. altilis prenylated flavonoids were selected as target ligands (artocarpin, artoindonesianin V, artonin M, cudraflavone A and cycloartobiloxanthone) and molecular targets from the SARS-CoV family were designated as receptors. Molecular docking was applied with the Lamarckian Genetic algorithm to measure the receptor-ligand orientation using AutoDock Vina software. The structural interactions of the receptor-ligand complexes were visualised using the Biovia Discovery Studio 4.5. Under all possible receptor-ligand combinations, the complexes’ minimum binding affinities (MBA) ranged from -5.5 to -9.1 kcal/mol and held by hydrophobic interactions, hydrogen bonds and electrostatic attractions. Receptor-ligand complexes with the least MBA (<-6.0 kcal/mol) along with strong structural interactions were validated by MD simulation using the GROMACS software. The 5RE4-artocarpin and 5RE4-artoindonesianin V showed the highest hydrophobic interactions at MBA=-6.6 kcal/mol and -6.4 kcal/mol, respectively. The trajectory analysis of 5RE4-artocarpin and 5RE4-artoindonesianin V complexes was fairly stable throughout a 50 ns MD simulation run. The findings conclude that artocarpin and artoindonesianin V are good potential SARS-CoV family receptor inhibitors.
Supporting literature

References

  1. Adewole, S. O., & Oiewole, J. O. (2007). Hyperglycaemic effect of Artocarpus communis Forst (Moraceae) root bark aqueous extract in Wistar rats: Cardiovascular topic. Cardiovascular Journal of Africa, 18(4), 221-227.
  2. Ali-Reza, A. S. M., Nasrin, M. S., Hossen, M. A., Rahman, M. A., Jantan, I., Haque, M. A., & Sobarzo-Sanchez, E. (2021). Mechanistic insight into immunomodulatory effects of food-functioned plant secondary metabolites. Critical Reviews in Food Science and Nutrition, 1-31. https://doi.org/10.1080/10408398.2021.2021138
  3. Amarasinghe, N. R., Jayasinghe, L., Hara, N., & Fujimoto, Y. Chemical constituents of the fruits of Artocarpus altilis. Biochemical Systematics and Ecology, 36(4), 323-325. https://doi.org/10.1016/j.bse.2007.09.007
  4. Aucoin, M., Cardozo, V., McLaren, M. D., Garber, A., Remy, D., Baker, J., Gratton, A., Kala, M. A., Monteiro, S., Warder, C., Perciballi, A., & Cooley, K. (2021). A systematic review on the effects of Echinacea supplementation on cytokine levels: Is there a role in COVID-19? Metabolism Open, 11, Article 100115. https://doi.org/10.1016/j.metop.2021.100115
  5. Baba, S., Chan, H. T., Kezuka, M., Inoue, T., & Chan, E. W. C. (2016). Artocarpus altilis and Pandanus tectorius: Two important fruits of Oceania with medicinal values. Emirates Journal of Food and Agriculture, 28(8), 531-539. https://doi.org/10.9755/ejfa.2016-02-207
  6. Bailly, C. (2021). Anticancer mechanism of artonin E and related prenylated flavonoids from the medicinal plant Artocarpus elasticus. Asian Journal of Natural Product Biochemistry, 19(2), 45-47. https://doi.org/10.13057/biofar/f190202
  7. Bhat, R., & Paliyath, G. (2016). Fruits of tropical climates: Biodiversity and dietary importance. In B. Caballero, P. M. Finglas & F. Toldrá (Eds.), Encyclopedia of Food and Health (pp. 138-143). Academic Press. https://doi.org/10.1016/B978-0-12-384947-2.00337-8
  8. Boson, B., Legros, V., Zhou, B., Siret, E., Mathieu, C., Cosset, F.-L., Lavillette, D. & Denolly, S. (2021). The SARS-CoV-2 envelope and membrane proteins modulate maturation and retention of the spike protein, allowing assembly of virus-like particles. Journal of Biological Chemistry, 296, Article 100111. https://doi.org/10.1074/jbc.RA120.016175
  9. Chang, S. K., Jiang, Y., & Yang, B. (2021). An update of prenylated phenolics: Food sources, chemistry and health benefits. Trends in Food Science & Technology, 108, 197-213. https://doi.org/10.1016/j.tifs.2020.12.022
  10. Cidade, H. M., Nacimento, M. S. J., Pinto, M. M. M., Kijjoa, A., Silva, A. M. S., & Herz, W. (2001). Artelastocarpin and carpelastofuran, two new flavones and cytotoxicities of prenyl flavonoids from Artocarpus elasticus against three cancer cell lines. Planta Medica, 67(9), 867-870. https://doi.org/10.1055/s-2001-18845
  11. Daley, O. O., Roberts-Nkrumah, L. B., & Alleyne, A. T. (2020). Morphological diversity of breadfruit [Artocarpus altilis (Parkinson) Fosberg] in the Caribbean. Scientia Horticulturae, 266, Article 109278. https://doi.org/10.1016/j.scienta.2020.109278
  12. Das, A., Ahmed, R., Akhtar, S., Begum, K., & Banu, S. (2021). An overview of basic molecular biology of SARS-CoV-2 and current COVID-19 prevention strategies. Gene Reports, 23, Aricle 101122. https://doi.org/10.1016/j.genrep.2021.101122
  13. Dawood, A. A. (2020). Mutated COVID-19 may foretell a great risk for mankind in the future. New Microbes and New Infections, 35, Article 100673. https://doi.org/10.1016/j.nmni.2020.100673
  14. De Vivo, M., Masetti, M., Bottegoni, G., & Cavalli, A. (2016). Role of molecular dynamics and related methods in drug discovery. Journal of Medicinal Chemistry, 59(9), 4035-4061. https://doi.org/10.1021/acs.jmedchem.5b01684.
  15. Demeke, C. A., Woldeyohanins, A. E., & Kifle, Z. D. (2021). Herbal medicine use for the management of COVID-19: A review article. Metabolism Open, 12, Article 100141. https://doi.org/10.1016/j.metop.2021.100141
  16. Dhurga, K., Gunasekaran, G., Senthilraja, P., Manivel, G., & Stalin, A. (2016). Molecular modeling and docking analysis of Pseudomonal bacterial proteins with Eugenol and its derivatives. Research Journal of Life Sciences, Bioinformatics, Pharmaceutical and Chemical Sciences, 2(1), 40-50.
  17. Fang, S. C., Hsu, C. L., Yu, Y. S., & Yen, G. C. (2008). Cytotoxic effects of new geranyl chalcone derivatives isolated from the leaves of Artocarpus communis in SW 872 human liposarcoma cells. Journal of Agricultural and Food Chemistry, 56(19), 8859-8868. https://doi.org/10.1021/jf8017436
  18. Hakim, E. H., Achmad, S. A., Juliawaty, L. D., Makmur, L., Syah, Y. M., Aimi, N., Kitajima, M., Takayaman, H., & Ghisalberti, E. L. (2006). Prenylated flavonoids and related compounds of the Indonesian Artocarpus (Moraceae). Journal of Natural Medicines, 60, 161-184. https://doi.org/10.1007/s11418-006-0048-0
  19. Hano, Y., Yamagami, Y., Kobayashi, M., Isohata, R., & Nomura, T. (1990). Artonins E and F, two new prenylflavones from the bark of Artocarpus communis Forst. Heterocycles, 31(5), 877-882. https://doi.org/10.3987/COM-90-5350
  20. Hari, A., Revikumar, K. G., & Divya, D. (2014). Artocarpus: A review of its phytochemistry and pharmacology. Journal of Pharma Search, 9(1), 7-12.
  21. Jalal, T. L., Ahmed, I. A., Mikail, M., Momand, L., Draman, S., Md Isa, M. L., Abdul Rasad, M. S. B., Omar, M. N., Ibrahim, M., & Wahab, R. A. (2015). Evaluation of antioxidant, total phenol and flavonoid content and antimicrobial activities of Artocarpus altilis (Breadfruit) of underutilisedd tropical fruit extracts. Applied Biochemistry and Biotechnology, 175(7), 3231-3243. https://doi.org/10.1007/s12010-015-1499-0
  22. Jamil, M. M. A., Ganeson. S., Mammam, H. B., & Wahab, R. A. (2018). Artocarpus altilis extract effect on cervical cancer cells. Materials Today: Proceedings, 5(7), 15559-15566. https://doi.org/10.1016/j.matpr.2018.04.163
  23. Jantan, I., Ahmad, W., & Bukhari, S. N. A. (2015). Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials. Frontiers in Plant Science, 6, Article 655. https://doi.org/10.3389/fpls.2015.00655
  24. Jorgensen, W. L. (2004). The many roles of computation in drug discovery. Science, 303(5665), 1813-1818. https://doi.org/10.1126/science.1096361
  25. Kaspi, S. N. A. M., Govender, N., & Mohamed-Hussein, Z. A. (2022). Brief communication: Caffeic acid derivatives and polymethoxylated flavonoids from cat’s whiskers (Orthosiphon stamineus) form stable complexes with SARS-CoV molecular targets: An In silico analysis. Pertanika Journal of Tropical Agricultural Science, 45(1), 235-244. https://doi.org/10.47836/pjtas.45.1.13
  26. Khaerunnisa, S., Kurniawan, H., Awaluddin, R., Suhartati, S., & Soetjipto, S. (2020). Potential inhibitor of COVID-19 main protease (Mpro) from several medicinal plant compounds by molecular docking study. Preprints, 2020, Article 2020030226. https://doi.org/10.20944/preprints202003.0226.v1
  27. Ko, H. H., Lu, Y. H., Yang, S. Z., Won, S. J., & Lin, C. N. (2005). Cytotoxic prenylflavonoids from Artocarpus elasticus. Journal of Natural Products, 68(11), 1692-1695. https://doi.org/10.1021/np050287j
  28. Lan, W. C., Tzeng, C. W., Lin, C. C., Yen, F. L., & Ko, H. H. (2013). Prenylated flavonoids from Artocarpus altilis: Antioxidant activities and inhibitory effects on melanin production. Phytochemistry, 89, 78-88.
  29. Lemkul, J. A. (2018). From proteins to perturbed Hamiltonians: A suite of tutorials for the GROMACS-2018 Molecular Simulation Package [Article v1.0]. Living Journal of Computational Molecular Science, 1(1), Article 5068. https://doi.org/10.33011/livecoms.1.1.5068
  30. Leng, L. Y., Nadzri, N. B., Yee, K. C., Razak, N. B. A., & Shaari, A. R. (2018). Antioxidant and total phenolic content of breadfruit (Artocarpus altilis) leaves. In MATEC Web of Conferences (Vol. 150, p. 06007).. EDP Sciences.
  31. Lin, J. A., Wu, C. H., Fang, S. C. & Yen, G. C. (2012). Combining the observation of cell morphology with the evaluation of key inflammatory mediators to assess the anti-inflammatory effects of geranyl flavonoid derivatives in breadfruit. Food Chemistry, 132(4), 2118-2125. https://doi.org/10.1016/j.foodchem.2011.12.070
  32. Liu, J., Sun, Y., Qi, J., Chu, F., Wu, H., Gao, F., Li, T., Yan, J., & Gao, G. F. (2010). The membrane protein of severe acute respiratory syndrome coronavirus acts as a dominant immunogen revealed by a clustering region of novel functionally and structurally defined cytotoxic T-lymphocyte epitopes. The Journal of Infectious Diseases, 202(8), 1171-1180. https://doi.org/10.1086/656315
  33. O’Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., & Hutchison, G. R. (2011). Open babel: An open chemical toolbox. Journal of Cheminformatics, 3, Article 33. https://doi.org/10.1186/1758-2946-3-33
  34. Page, M. L. (2021). Climate change: Breadfruit could be food of future as planet warms. New Scientist, 251(3356), 11. https://doi.org/10.1016/S0262-4079(21)01817-0
  35. Paraiso, I. L., Revel, J. S., & Stevens, J. F. (2020). Potential use of polyphenols in the battle against COVID-19. Current Opinion in Food Science, 32, 149-155. https://doi.org/10.1016/j.cofs.2020.08.004
  36. Pronk, S., Páll, S., Schulz, R., Larsson, P., Bjelkmar, P., Apostolov, R., Shirts, M. R., Smith, J. C., Kasson, P. M., van der Spoel, D., Hess, B., & Lindahl, E. (2013). GROMACS 4.5: A high- throughput and highly parallel open source molecular simulation toolkit. Bioinformatics, 29(7), 845-854. https://doi.org/10.1093/bioinformatics/btt055
  37. Ragone, D. (2018). Breadfruit-Artocarpus altilis (Parkinson) Fosberg. In S. Rodrigues, O., E. de Oliveira Silva & E. S. de Brito (Eds.), Exotic Fruits (pp. 53-60). Academic Press. https://doi.org/10.1016/B978-0-12-803138-4.00009-5
  38. Rehman, S. U., Rehman, S. U., & Yoo, H. H. (2021). COVID-19 challenges and its therapeutics. Biomedicine & Pharmacotherapy, 142, Article 112015. https://doi.org/10.1016/j.biopha.2021.112015
  39. Septama, A. W., Jantan, I., & Panichayupakaranant, P. (2018). Flavonoids of Artocarpus heterophyllus Lam. heartwood inhibit the innate immune responses of human phagocytes. Journal of Pharmacy and Pharmacology, 70(9), 1242-1252. https://doi.org/10.1111/jphp.12952
  40. Shah, M. K. K., Sirat, H. M., Jamil, S., & Jalil, J. (2016). Flavonoids from the bark of Artocarpus integer var. silvestris and their anti-inflammatory properties. Natural Product Communications, 11(9), 1275-1278. https://doi.org/10.1177/1934578X1601100921
  41. Shamaun, S. S., Rahmani, M., Hashim, N. M., Ismail, H. B. M., Sukari, M. A., Lian, G. E. C., & Go, R. (2010). Prenylated flavones from Artocarpus altilis. Journal of Natural Medicines, 64, 478-481. https://doi.org/10.1007/s11418-010-0427-4
  42. Shi, S., Li, J., Zhao, X., Liu, Q., & Song, S. J. (2021). A comprehensive review: Biological activity, modification and synthetic methodologies of prenylated flavonoids. Phytochemistry, 191, Article 112895. https://doi.org/10.1016/j.phytochem.2021.112895
  43. Shieh, W. L., & Lin, C. N. (1992). A quinonoid pyranobenzoxanthone and pyranodihydrobenzoxanthone from Artocarpus communis. Phytochemistry, 31(1), 364-367. https://doi.org/10.1016/0031-9422(91)83081-U
  44. Shimizu, K., Kondo, R., Sakai, K., Lee, S. H., & Sato, H. (1998). The Inhibitory Components from Artocarpus incisus on Melanin Biosynthesis. Planta Medica, 64(5), 408-412. https://doi.org/10.1055/s-2006-957470
  45. Sikarwar, M. S., Hui, B. J., Subramaniam, K., Valeisamy, B. D., Yean, L. K., & Balaji, K. (2014). A review on Artocarpus altilis (Parkinson) Fosberg (breadfruit). Journal of Applied Pharmaceutical Science, 4(08), 091-097.
  46. Skariyachan, S., Gopal, D., Chakrabarti, S., Kempanna, P., Uttarkar, A., Muddebihalkar, A. G., & Niranjan, V. (2020). Structural and molecular basis of the interaction mechanism of selected drugs towards multiple targets of SARS-CoV-2 by molecular docking and dynamic simulation studies-deciphering the scope of repurposed drugs. Computational Biology Medicine, 126, Article 104054.
  47. Sofoini, T., Donno, D., Jeannoda, V., Rakotoniaina, E., Hamidou, S., Achmet, S. M., Solo, N. R., Afraitane, K., Giacoma, C., & Beccaro, G. L. (2018). Bioactive compounds, nutritional traits, and antioxidant properties of Artocarpus altilis (Parkinson) fruits: Exploiting potential functional food for food security on the Comoros Islands. Journal of Food Quality, 2018, Article 5697928. https://doi.org/10.1155/2018/5697928
  48. Suhartati, T., Yandri, Y., & Hadi, S. (2008).The bioactivity test of Artonin E from the bark of Artocarpus rigida Blume. European Journal of Scientific Research, 23(2), 330-337.
  49. Tang, Y., Liu, J., Zhang, D., Xu, Z., Ji, J., & Wen, C. (2020). Cytokine storm in COVID-19 : The current evidence and treatment strategies. Frontiers in Immunology, 11, Article 1708. https://doi.org/10.3389/fimmu.2020.01708
  50. Trott, O., & Olson, A. J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31(2), 455-461. https://doi.org/10.1002/jcc.21334
  51. Vanommeslaeghe, K., Hatcher, E., Acharya, C., Kundu, S., Zhong, S., Shim, J., Darian, E., Guvench, O., Lopes, P., Vorobyov, I., & Mackerell Jr, A. D. (2009). CHARMM general force field: A force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. Journal of Computational Chemistry, 31(4), 671-690. https://doi.org/10.1002/jcc.21367
  52. Wei, B. L., Weng, J. R., Chiu, P. H., Hung, C. F., Wang, J. P. & Lin, C. N. (2005). Anti-inflammatory flavonoids from Artocarpus heterophyllus and Artocarpus communis. Journal of Agricultural and Food Chemistry, 53, 3867-3871. https://doi.org/10.1021/jf047873n
  53. Weng, J. R., Chan, S. C., Lu, Y. H., Lin, H. C., Ko, H. H., & Lin, C. N. (2006). Antiplatelet prenylflavonoids from Artocarpus communis. Phytochemistry, 67(8), 824-829. https://doi.org/10.1016/j.phytochem.2006.01.030
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