Effect of Alkaloids on SARS-CoV-2

Abstract

The use of herbs in treatment has started with the history of humanity and a significant number of effective drugs are being developed from herbal sources. Primary and secondary metabolites, which are natural products produced by plants, are the most basic products of the industry directly or indirectly. One of these groups is alkaloids. Alkaloids show antiviral effects in viral diseases. COVID-19, which started in China and spread to many countries, has become an epidemic that threatens all humanity worldwide as "Coronavirus Pandemic". No reliable and certified drug has yet been developed for this virus. Recent important research shows that plant-based substances can be potential candidates for developing effective and safe drugs against this virus. Referring to such recent studies, this study primarily shows that the antiviral potentials of some alkaloids especially quinine and artemisinin and its derivatives. In addition, the importance of antiviral plant substances in the development of a broad-spectrum drug for SARS-CoV-2 is emphasized.

Keywords

• SARS-CoV-2
• COVID-19
• Alkaloid
• Quinine
• Artemisinin

References

1. [1] Li, G., Fan, Y., Lai, Y., Han, T., Li, Z., Zhou, P. et al. (2020). Coronavirus infections and immune responses, J. Med. Virol. 92(4): 424-32.
2. [2] Chan, J. F., Lau, S. K., To, K. K., Cheng, V. C., Woo, P. C. And Yuen, K. Y (2015). Middle East respiratory syndrome coronavirus: Another zoonotic betacoronavirus causing SARS-like disease, Clin. Microbiol., 28(2), 465-522.
3. [3] Desbois, D., Vaghefi, P., Savary, J., Dussaix, E. and Roque-Afonso, A. M. (2008). Sensitivity of a rapid immuno-chromatographic test for hepatitis C antibodies detection, J. Clin. Virol., 41(2): 129-133.
4. [4] Ababneh, M., Alrwashdeh, M., Khalifeh, M. (2019). Recombinant adenoviral vaccine encoding the spike 1 subunit of the Middle East Respiratory Syndrome Coronavirus elicits strong humoral and cellular immune responses in mice, Vet World., 12(10): 1554-1562.
5. [5] Mukherjee, A., Ahmad, M., Frenia, D. (2020.) A coronavirus disease 2019 (COVID-19) patient with multifocal pneumonia treated with hydroxychloroquine, Cureus, 12(3); e7473.
6. [6] Guo, Y-R., Cao, Q-D., Hong, Z-S. et.al. (2020). The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak: an update on the status, Mil Med Res.,7:11.
7. [7] Wujtewicz, M., Dylczyk-Sommer, A., Aszkiełowicz, A., Zdanowski, S., Piwowarczyk, S., Owczuk R. (2020). COVID-19: what should anaethesiologists and intensivists know about it?, Anaesthesiol Intensive Ther, 52:34-41.
8. [8] Holshue, M. L., DeBolt, C., Lindquist, S., et. al. (2020). First case of 2019 novel coronavirus in the United States, N Engl J Med., 382:929-936.

9. [9] Salehi, S., Abedi, A., Balakrishnan, S. And Gholamrezanezhad, A. (2020). Coronavirus disease 2019 (COVID-19): A systematic review of imaging findings in 919 patients, AJR, 215;87-93.
10. [10] Önmez, H. (2007). Papaver somniferum Bitkisinden Elde Edilen Alkaloitlerin Ekstraksiyonunda Kullanılan Cozucu ve Metodların Karsılastırılması, Master Thesis, Selçuk University Institute of Science and Technology, Konya.
11. [11] Zulak, K. G., Liscombe, D. K., Ashihara and Facchini, P. J. (2006). Plant Secondary Metabolites In: Alkaloids, Blackwell Publishing, 102-136.
12. [12] Gürkök, T., Parmaksız İ., Boztepe G., and Kaymak E. (2010) “Haşhaş (Papaver somniferum L.) Bitkisinde Alkaloid Biyosentez Mekanizması, BiyoTeknoloji Elektronik Dergisi, 1(2) 31-45.
13. [13] Facchini, P. J. and Bird D. A. (1997). Developmental regulation of benzylisoquinoline alkaloid biosynthesis in opium poppy plants and tissue cultures,, In vitro Cel. Dev. Biol., 34; 69-79.
14. [14] Chin, L.W., Cheng, Y. and Lin, S. (2010). Anti-herpes simplex virus effects of berberine from Coptidis rhizoma, a major component of a Chinese herbal medicine, Ching-Wei-San. Arch. Virol., 155; 1933–1941.
15. [15] Varghese, F. S., Kaukinen, P., Gläsker, S, Bespalov, M., Hanski, L., Wennerberg, K., Kümmerer, B.M. and Ahola, T. (2016). Discovery of berberine, abamectin and ivermectin as antivirals against chikungunya and other alphaviruses, Antiviral Res., 126; 117–124.
16. [16] Kim, D.E.., Min, J. S., Jang. M. S., Lee, J. Y., Shin, Y. S. and Song, J. H. (2019). Natural bis-benzylisoquinoline alkaloids—Tetrandrine, fangchinoline, and cepharanthine, inhibit human coronavirus OC43 infection of MRC-5 human lung cells. Biomolecules, 9(11); 696.
17. [17]Jia, F., Zou, G., Fan, J. and Yuan, Z. (2010) Identification of palmatine as an inhibitor of West Nile virüs, Arch. Virol., 155; 1325–1329.
18. [18] Ho, Y. J., Lu, J. W., Huang, J. L. and Lai, Z. Z. (2019). Palmatine inhibits Zika virus infection by disrupting virus binding, entry, and stability, Biochem. Biophys. Res. Commun., 518; 732–738.
19. [19] Wyk, B.E. and Wink, M. (2017) Medicinal Plants of the World, 2nd ed.; CABI: Wallingford, UK.
20. [20] Croaker, A., King, G. J., Pyne, J. H., Anoopkumar-Dukie, S. and Liu, L. (2016) Sanguinaria canadensis: Traditional medicine, phytochemical composition, biological activities and current uses, Int. J. Mol. Sci., 17, 1414.
21. [21] Bleasel, M. D. and Peterson, G. M. (2020) Emetine, ipecac, ipecac alkaloids and analogues as potential antiviral agents for coronaviruses. Pharmaceuticals, 13(3); 51.
22. [22] Gurung, P. and De, P. (2017). Spectrum of biological properties of cinchona alkaloids: A brief review, J. Pharmacogn. Phytochem., 6(4); 162-166.
23. [23] D’Alessandro, S., Scaccabarozzi, D., Signorini, L., Perego, F., Ilboudo, D.P., Ferrante, P., Delbue, S. (2020). The use of antimalarial drugs against viral infection, Microorganisms, 8(1); 85.
24. [24] Salako, L. A. and Sowunmi, A. (1992). Disposition of quinine in plasma, red blood cells and saliva after oral and intravenous administration to healthy adult Africans, Eur J Clin Pharmacol, 42(2); 171-174.
25. [25] White, N. J. (1996). The treatment of malaria, N Engl J Med, 335(11); 800-806.
26. [26] Esamai, F., Ayuo, P., Owino-Ongor, W., Rotich, J., Ngindu. A, et. al. (2000) Rectal dihydroartemisinin versus intravenous quinine in the treatment of severe malaria: A randomized clinical trial, East Afr. Med. J., 77(5): 273-278.
27. [27] Jamaludin, A., Mohamed, M., Navaratnam, V., Mohamed, N., Yeoh, E., Wernsdorfer, W. (1988). Single-dose comparative kinetics and bioavailability study of quinine hydrochloride, quinidine sulfate and quinidine bisulfate sustained-release in healthy male volunteers, Acta Leiden, 57(1):39-46.
28. [28] White, N. J. (1992). Antimalarial pharmacokinetics and treatment regimens, Br. J. Clin. Pharmacol, 34(1); 1-10.
29. [29] Savarino, A., Boelaert, J. R., Cassone, A., Majori, G., Cauda, R. (2003). Effects of chloroquine on viral infections: An old drug against today's diseases? Lancet. Infect. Dis., 3; 722-727.
30. [30] Yan, Y., Zou, Z., Sun, Y., Li, X., Xu, K. F., Wei, Y., Jin, N., Jiang, C. (2013) Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model, Cell Res., 23; 300-302.
31. [31] McKee, D. L. Sternberg A., Strange U., Laufer S., Naujokat C. (2020). Candidate drugs against SARS-CoV-2 and COVID-19, Pharmacol. Res., 157; 104859.
32. [32] Cortegiani, A., Ingoglia, G., Ippolito, M., Giarratano, A. and Einav, S. (2020). A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19, J.Crit. Care, 9441(20); 30390-7.
33. [33] Chan, K.W., Wong, V.T. and Tang, S.C.W. (2020). COVID-19: An update on the epidemiological,clinical, preventive and therapeutic evidence and guidelines of integrative Chinese-Western medicine for the management of 2019 novel coronavirus disease, Am. J. Chin. Med., 48(3): 737-762.
34. [34] Gautret, P. et al. (2020). Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial, Int. J. Antimicrob. Agents, 105949.
35. [35] Cascella, M., Rajnik, M., Cuomo, A., Dulebohn, S. C. and Di Napoli, R. (2020). Features, evaluation and treatment Coronavirus (COVID-19), Stat Pearls [Internet], Available from: https://www.ncbi.nlm.nih.gov/books/NBK554776/.
36. [36] Wang, M., Cao, R., Zhang, L., Yang, X., Liu, J., Xu, M., et al. (2020). Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Research, 30(3); 269–271.
37. [37] Gao J., Tian Z. and Yang X. (2020). Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID- 19 associated pneumonia in clinical studies, Biosci Trends. 14(1); 72-73.
38. [38] Yao, X., Ye, F., Zhang, M., Cui, C., Huang, B., Nui, P. et al. (2020). In vitro antiviral activityand projection of optimized dosing design of hydroxychloroquine for the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Clin.Infect. Dis. 71(15); 732-739.
39. [39] Lestari, K., Sitorus, T., Megantara, S. and Levita, J. (2020). Molecular Docking of Quinine, Chloroquine and Hydroxychloroquine to Angiotensin Converting Enzyme 2 (ACE2) Receptor for Discovering New Potential COVID-19 Antidote, J Adv Pharm Edu Res, 10(2): 1-4.
40. [40] Große, M., Ruetalo, N., Businger, R., Rheber, S., Setz, C., Rauch, P., Auth, J., Brysch, E., Schindler, M. and Schubert, U. (2020). Evidence That Quinine Exhibits Antiviral Activity against SARS-CoV-2 Infection In Vitro. Preprints, 070102.
41. [41] Huang C., et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China, Lancet, 395(10223); 497-6.
42. [42] Law S., Leung AW. and Xu C. (2020). Is the traditional Chinese herb “Artemisia annua” possible to fight against COVID-19?, Integr Med Res, 9(3); 100474.
43. [43] Mannan, A., Ahmed, I., Arshad, W. and Asim, M. F. (2010). Survey of artemisinin production by diverse Artemisia species in northern Pakistan, Malaria Journal, 9: 310. [44] World malaria report 2019. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO.
44. [45] Zhang, S. and Gerhard, G.S. (2009). Heme Mediates Cytotoxicity from Artemisinin and Serves as a General Anti-Proliferation Target, Plos One, 4(10): 7472.
45. [46] Gharib, A., Faezizadeh, Z., Ali Reza, S., Namin, M. and Saravani, R. (2015). Experimental treatment of breast cancer-bearing BALB/c mice by artemisinin and transferrin-loaded magnetic nanoliposomes, Pharmacognosy Magazine, Suppl. (S1): 117-122.
46. [47] Kim, W. S., Choi, W. J., Lee, S., Kim, W. J., Lee, D. C. and Sohn, U. D. (2015). Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L, The Korean journal of physiology & pharmacology: official journal of the Korean Physiological Society and the Korean Society of Pharmacology, 19(1): 21–27.
47. [48] Benatoui, P. and Galabert J.L. (2020). Assessing the potential of Artemisia annua in the fight against COVID-19, https://lavierebelle.org/evaluer-le-potentiel-de-l?lang=en
48. [49] Zhou, P., et al. (2020). A pneumonia outbreak associated with a new coronavirus of probable bat origin, Nature, 579 (7798): 270–273.
49. [50] Cheong, DHJ., Tan, DWS., Wong, FWS. and Tran, T. (2020). Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases, Pharmacol Res., 158: 104901.