Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2?

doi:10.1007/s13659-020-00250-4

摘要/Abstract

摘要： New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic (COVID-19) declared by WHO. Coronavirus disease 2019 (COVID-19) is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2). SARS-CoV-2 is akin to SARS-CoV, which was the causative agent of severe acute respiratory syndrome (SARS) in 2002 as well as to that of Middle East respiratory syndrome (MERS) in 2012. SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member of β-coronaviruses. It has a positive-sense single-stranded RNA with the largest RNA genome. Since its genomic sequence has a notable similarity to that of SARS-CoV, antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment. In order to combat SARS-CoV-2, many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide. In this sense, medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses. In the present review, plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.

关键词: Coronavirus, SARS-CoV, Medicinal plants, Natural products, Antiviral

Abstract: New coronavirus referred to SARS-CoV-2 has caused a worldwide pandemic (COVID-19) declared by WHO. Coronavirus disease 2019 (COVID-19) is an infectious disease with severe acute respiratory syndrome caused by coronavirus-2 (SARS-CoV-2). SARS-CoV-2 is akin to SARS-CoV, which was the causative agent of severe acute respiratory syndrome (SARS) in 2002 as well as to that of Middle East respiratory syndrome (MERS) in 2012. SARS-CoV-2 has been revealed to belong to Coronaviridiae family as a member of β-coronaviruses. It has a positive-sense single-stranded RNA with the largest RNA genome. Since its genomic sequence has a notable similarity to that of SARS-CoV, antiviral drugs used to treat SARS and MERS are now being also applied for COVID-19 treatment. In order to combat SARS-CoV-2, many drug and vaccine development studies at experimental and clinical levels are currently conducted worldwide. In this sense, medicinal plants and the pure natural molecules isolated from plants have been reported to exhibit significant inhibitory antiviral activity against SARS-CoV and other types of coronaviruses. In the present review, plant extracts and natural molecules with the mentioned activity are discussed in order to give inspiration to researchers to take these molecules into consideration against SARS-CoV-2.

Key words: Coronavirus, SARS-CoV, Medicinal plants, Natural products, Antiviral

Ilkay Erdogan Orhan, F. Sezer Senol Deniz. Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2?[J]. 应用天然产物, 2020, 10(4): 171-186.

Ilkay Erdogan Orhan, F. Sezer Senol Deniz. Natural Products as Potential Leads Against Coronaviruses: Could They be Encouraging Structural Models Against SARS-CoV-2?[J]. Natural Products and Bioprospecting, 2020, 10(4): 171-186.

参考文献

1. S.R. Weiss, S. Navas-Martin, Microbiol. Mol. Biol. Rev. 69, 635-664 (2005)
2. D. Groneberg, R. Hilgenfeld, P. Zabel, Respir. Res. 6, 1-16 (2005)
3. T.G. Ksiazek, D. Erdman, C.S. Goldsmith, S.R. Zaki, T. Peret, S. Emery, S. Tong, C. Urbani, J.A. Comer, W. Lim, P.E. Rollin, S.F. Dowell, A.E. Ling, C.D. Humphrey, W.J. Shieh, J. Guarner, C.D. Paddock, P. Rota, B. Fields, J. Derisi, J.Y. Yang, N. Cox, J.M. Hughes, J.W. LeDuc, W.J. Bellini, L.J. Anderson, N. Engl, J. Med. 348, 1953-1966 (2003)
4. K.G. Andersen, A. Rambaut, W.I. Lipkin, E.C. Holmes, R.F. Garry, Nat. Med. 26, 450-455 (2020)
5. T. Zhang, Q. Wu, Z. Zhang, Curr. Biol. 30, 1346-1351 (2020)
6. F.L. Tort, M. Castells, J. Cristina, Virus Res. (2020). https://doi.org/10.1016/j.virusres.2020.197976
7. R. Lu, X. Zhao, J. Li, P. Niu, B. Yang, H. Wu et al., Lancet 395, 565-574 (2020)
8. M. Ceccarelli, M. Berretta, E. Venanzi Rullo, G. Nunnari, B. Cacopardo, Eur. Rev. Med. Pharmacol. Sci. 24, 2781-2783 (2020)
9. C.A. Devaux, J.M. Rolain, P. Colson, D. Raoult, Int. J. Antimicrob. Agents 55, 105938 (2020)
10. M. Costanzo, M.A.R. De Giglio, G.N. Roviello, Curr. Med. Chem. (2020). https://doi.org/10.2174/0929867327666200416131117
11. J. Stebbing, A. Phelan, I. Griffin, C. Tucker, O. Oechsle, D. Smith, P. Richardson, Lancet Infect. Dis. 20, 400-402 (2020)
12. H. Lu, Biosci. Trends 14, 69-71 (2020)
13. A.R. McCutcheon, T.E. Roberts, E. Gibbons, S.M. Ellis, L.A. Babiuk, R.E. Hancock, G.H. Towers, J. Ethnopharmacol. 49, 101-110 (1995)
14. G.J. Kotwal, J.N. Kaczmarek, S. Leivers, Y.T. Ghebremariam, A.P. Kulkarni, G. Bauer, C. De Beer, W. Preiser, A.R. Mohamed, Ann. NY Acad. Sci. 1056, 293-302 (2005)
15. H.Y. Kim, H.S. Shin, H. Park, Y.C. Kim, Y.G. Yun, S. Park, H.J. Shin, K. Kim, J. Clin. Virol. 41, 122-128 (2008)
16. H.Y. Kim, E.Y. Eo, H. Park, Y.C. Kim, S. Park, H.J. Shin, K. Kim, Antiviral Ther. 15, 697-709 (2010)
17. M.R. Loizzo, A.M. Saab, R. Tundis, G.A. Statti, F. Menichini, I. Lampronti, R. Gambari, J. Cinatl, H.W. Doerr, Chem. Biodivers. 5, 461-470 (2008)
18. C.J. Chen, M. Michaelis, H.K. Hsu, C.C. Tsai, K.D. Yang, Y.C. Wu, J. Cinatl Jr., H.W. Doerr, J. Ethnopharmacol. 120, 108-111 (2008)
19. M. Zhuang, H. Jiang, Y. Suzuki, X. Li, P. Xiao, T. Tanaka, H. Ling, B. Yang, H. Saitoh, L. Zhang, C. Qin, K. Sugamura, T. Hattori, Antiviral Res. 82, 73-81 (2009)
20. W. Luo, X. Su, S. Gong, Y. Qin, W. Liu, J. Li, H. Yu, Q. Xu, Biosci. Trends 3, 124-126 (2009)
21. H.S. Yook, K.H. Kim, J.E. Park, H.J. Shin, Am. J. Chin. Med. 38, 937-948 (2010)
22. M. Ulasli, S.A. Gurses, R. Bayraktar, O. Yumrutas, S. Oztuzcu, M. Igci, Y.Z. Igci, E.A. Cakmak, A. Arslan, Mol. Biol. Rep. 41, 1703-1711 (2014)
23. C. Chen, D.M. Zuckerman, S. Brantley, M. Sharpe, K. Childress, E. Hoiczyk, A.R. Pendleton, BMC Vet. Res. 10, 24 (2014)
24. R. Lelešius, A. Karpovaitė, R. Mickienė, T. Drevinskas, N. Tiso, O. Ragažinskienė, L. Kubilienė, A. Maruška, A. Šalomskas, BMC Vet. Res. 15, 178 (2019)
25. C. Fiore, M. Eisenhut, R. Krausse, E. Ragazzi, D. Pellati, D. Armanini, J. Bielenberg, Phytother. Res. 22, 141-148 (2005)
26. J. Cinatl, B. Morgenstern, G. Bauer, P. Chandra, H. Rabenau, H.W. Doerr, Lancet 361, 2045-2046 (2003)
27. C.Y. Wu, J.T. Jan, S.H. Ma, C.J. Kuo, H.F. Juan, Y.S. Cheng, H.H. Hsu, H.C. Huang, D. Wu, A. Brik, F.S. Liang, R.S. Liu, J.M. Fang, S.T. Chen, P.H. Liang, C.H. Wong, Proc. Natl. Acad. Sci. USA 101, 10012-10017 (2004)
28. J.W. Kim, T.K. Ha, H. Cho, E. Kim, S.H. Shim, J.L. Yang, W.K. Oh, Bioorg. Med. Chem. Lett. 27, 3019-3025 (2017)
29. P.W. Cheng, L.T. Ng, L.C. Chiang, C.C. Lin, Clin. Exp. Pharmacol. Physiol. 33, 612-616 (2006)
30. L. Yi, Z. Li, K. Yuan, X. Qu, J. Chen, G. Wang, H. Zhang, H. Luo, L. Zhu, P. Jiang, L. Chen, Y. Shen, M. Luo, G. Zuo, J. Hu, D. Duan, Y. Nie, X. Shi, W. Wang, Y. Han, T. Li, Y. Liu, M. Ding, H. Deng, X. Xu, J. Virol. 78, 11334-11339 (2004)
31. C.W. Lin, F.J. Tsai, C.H. Tsai, C.C. Lai, L. Wan, T.Y. Ho, C.C. Hsieh, P.D. Chao, Antiviral Res. 68, 36-42 (2005)
32. H. Li, J. Wu, Z. Zhang, Y. Ma, F. Liao, Y. Zhang, G. Wu, Phytother. Res. 25, 338-342 (2011)
33. Y.B. Ryu, H.J. Jeong, J.H. Kim, Y.M. Kim, J.Y. Park, D. Kim, T.T. Nguyen, S.J. Park, J.S. Chang, K.H. Park, M.C. Rho, W.S. Lee, Bioorg. Med. Chem. 18, 7940-7947 (2010)
34. D.W. Kim, K.H. Seo, M.J. Curtis-Long, K.Y. Oh, J.W. Oh, J.K. Cho, K.H. Lee, K.H. Park, J. Enzyme Inhib. Med. Chem. 29, 59-63 (2014)
35. J.K. Cho, M.J. Curtis-Long, K.H. Lee, D.W. Kim, H.W. Ryu, H.J. Yuk, K.H. Park, Bioorg. Med. Chem. 21, 3051-3057 (2013)
36. Y.H. Song, D.W. Kim, M.J. Curtis-Long, H.J. Yuk, Y. Wang, N. Zhuang, K.H. Lee, K.S. Jeon, K.H. Park, Biol. Pharm. Bull. 37, 1021-1028 (2014)
37. J.Y. Park, H.J. Yuk, H.W. Ryu, S.H. Lim, K.S. Kim, K.H. Park, Y.B. Ryu, W.S. Lee, J. Enzym. Inhib. Med. Chem. 32, 504-515 (2017)
38. Y.C. Shen, L.T. Wang, A.T. Khalil, L.C. Chiang, P.W. Chem, Pharm. Bull. 53, 244-247 (2005)
39. D.H. Zhang, K.L. Wu, X. Zhang, S.Q. Deng, B. Peng, J. Integr. Med. 18, 152-158 (2020)
40. M.T. Ul Qamar, S.M. Alqahtani, M.A. Alamri, L.L. Chen, J. Pharm. Anal. (2020). https://doi.org/10.1016/j.jpha.2020.03.009
41. S.Y. Li, C. Chen, H.Q. Zhang, H.Y. Guo, H. Wang, L. Wang, X. Zhang, S.N. Hua, J. Yu, P.G. Xiao, R.S. Li, X. Tan, Antiviral Res. 67, 18-23 (2005)
42. C.W. Yang, Y.Z. Lee, I.J. Kang, D.L. Barnard, J.T. Jan, D. Lin, C.W. Huang, T.K. Yeh, Y.S. Chao, S.J. Lee, Antiviral Res. 88, 160-168 (2010)
43. K.B. Kang, G. Ming, G.J. Kim, T.K. Ha, H. Choi, W.K. Oh, S.H. Sung, Phytochemistry 119, 90-95 (2015)
44. C.C. Wen, Y.H. Kuo, J.T. Jan, P.H. Liang, S.Y. Wang, H.G. Liu, C.K. Lee, S.T. Chang, C.J. Kuo, S.S. Lee, C.C. Hou, P.W. Hsiao, S.C. Chien, L.F. Shyur, N.S. Yang, J. Med. Chem. 50, 4087-4095 (2007)
45. J.Y. Park, J.H. Kim, Y.M. Kim, H.J. Jeong, D.W. Kim, K.H. Park, H.J. Kwon, S.J. Park, W.S. Lee, Y.B. Ryu, Bioorg. Med. Chem. 20, 5928-5935 (2012)
46. F.R. Chang, C.T. Yen, M. El-Shazly, W.H. Lin, M.H. Yen, K.H. Lin, Y.C. Wu, Nat. Prod. Commun. 7, 1415-1417 (2012)
47. J.L. Yang, T.K. Ha, B. Dhodary, E. Pyo, N.H. Nguyen, H. Cho, E. Kim, W.K. Oh, J. Med. Chem. 58, 1268-1280 (2015)
48. L.L. Liu, T.K. Ha, W. Ha, W.K. Ohi, J.L. Yangi, Y.P. Shi, J. Nat. Prod. 80, 298-307 (2017)
49. T.Y. Ho, S.L. Wu, J.C. Chen, C.C. Li, C.Y. Hsiang, Antiviral Res. 74, 92-101 (2007)
50. L.E. Hsieh, C.N. Lin, B.L. Su, T.R. Jan, C.M. Chen, C.H. Wang, D.S. Lin, C.T. Lin, L.L. Chueh, Antiviral Res. 88, 25-30 (2010)
51. Q.Y. Yang, X.Y. Tian, W.S. Fang, J. Asian Nat. Prod. Res. 9, 59-65 (2007)
52. J.Y. Park, J.A. Ko, D.W. Kim, Y.M. Kim, H.J. Kwon, H.J. Jeong, C.Y. Kim, K.H. Park, W.S. Lee, Y.B. Ryu, J. Enzyme Inhib. Med. Chem. 31, 23-30 (2016)
53. J.Y. Park, H.J. Jeong, J.H. Kim, Y.M. Kim, S.J. Park, D. Kim, K.H. Park, W.S. Lee, Y.B. Ryu, Biol. Pharm. Bull. 35, 2036-2042 (2012)
54. E. Keyaerts, L. Vijgen, C. Pannecouque, E. Van Damme, W. Peumans, H. Egberink, J. Balzarini, M. Van Ranst, Antiviral Res. 75, 179-187 (2007)
55. J.H. Lee, J.S. Park, S.W. Lee, S.Y. Hwang, B.E. Young, H.J. Choi, Virus Res. 195, 148-152 (2015)
56. P. Zhang, X. Liu, H. Liu, W. Wang, X. Liu, X. Li, X. Wu, Microb. Pathog. 114, 124-128 (2018)
57. P. Zhang, J. Wang, W. Wang, X. Liu, H. Liu, X. Li, X. Wu, Microb. Pathog. 111, 81-85 (2017)
58. X. Ma, S. Bi, Y. Wang, X. Chi, S. Hu, Poult. Sci. 98, 3548-3556 (2019)
59. P.Q. Nguyen, J.S. Ooi, N.T. Nguyen, S. Wang, M. Huang, D.X. Liu, J.P. Tam, J. Biol. Chem. 290, 31138-31150 (2015)

[1]	Hesham R. El-Seedi, Mohamed S. Refaey, Nizar Elias, Mohamed F. El-Mallah, Faisal M. K. Albaqami, Ismail Dergaa, Ming Du, Mohamed F. Salem, Haroon Elrasheid Tahir, Maria Dagliaa, Nermeen Yosri, Hongcheng Zhang, Awg H. El-Seedi, Zhiming Guo, Shaden A. M. Khalifa. Marine natural products as a source of novel anticancer drugs: an updated review (2019-2023)[J]. 应用天然产物, 2025, 15(2): 13-13.
[2]	Xiaoxia Gu, Xiaotian Zhang, Xueke Zhang, Xinyu Wang, Weiguang Sun, Yonghui Zhang, Zhengxi Hu. Unveiling the mechanism of action of a novel natural dual inhibitor of SARS-CoV-2 Mpro and PLpro with molecular dynamics simulations[J]. 应用天然产物, 2025, 15(1): 3-3.
[3]	María I. Osella, Mario O. Salazar, Carlos M. Solís, Ricardo L. E. Furlan. New semisynthetic α-glucosidase inhibitor from a doubly-chemically engineered extract[J]. 应用天然产物, 2025, 15(1): 4-4.
[4]	Ahmed H. Elbanna, Xinhui Kou, Dilip V. Prajapati, Surasree Rakshit, Rebecca A. Butcher. Discovery of a parallel family of euglenatide analogs in Euglena gracilis[J]. 应用天然产物, 2025, 15(1): 10-10.
[5]	Song-Yu Hou, Bing-Chao Yan, Han-Dong Sun, Pema-Tenzin Puno. Recent advances in the application of [2+2] cycloaddition in the chemical synthesis of cyclobutane-containing natural products[J]. 应用天然产物, 2024, 14(5): 37-37.
[6]	Felaine Anne Sumang, Alan Ward, Jeff Errington, Yousef Dashti. Hibiscus acid and hydroxycitric acid dimethyl esters from Hibiscus flowers induce production of dithiolopyrrolone antibiotics by Streptomyces Strain MBN2-2[J]. 应用天然产物, 2024, 14(5): 40-40.
[7]	Chunsong Hu. Marine natural products and human immunity: novel biomedical resources for anti-infection of SARS-CoV-2 and related cardiovascular disease[J]. 应用天然产物, 2024, 14(2): 2-2.
[8]	Shohreh Ariaeenejad, Javad Gharechahi, Mehdi Foroozandeh Shahraki, Fereshteh Fallah Atanaki, Jian-Lin Han, Xue-Zhi Ding, Falk Hildebrand, Mohammad Bahram, Kaveh Kavousi, Ghasem Hosseini Salekdeh. Precision enzyme discovery through targeted mining of metagenomic data[J]. 应用天然产物, 2024, 14(1): 7-7.
[9]	Daniel W. Armstrong, Alain Berthod. Occurrence of D-amino acids in natural products[J]. 应用天然产物, 2023, 13(6): 47-47.
[10]	Dalila Carbone, Carmela Gallo, Genoveffa Nuzzo, Giusi Barra, Mario Dell'Isola, Mario Affuso, Olimpia Follero, Federica Albiani, Clementina Sansone, Emiliano Manzo, Giuliana d'Ippolito, Angelo Fontana. Marine natural product lepadin A as a novel inducer of immunogenic cell death via CD91-dependent pathway[J]. 应用天然产物, 2023, 13(5): 34-34.
[11]	Phanankosi Moyo, Luke Invernizzi, Sephora M. Mianda, Wiehan Rudolph, Warren A. Andayi, Mingxun Wang, Neil R. Crouch, Vinesh J. Maharaj. Leveraging off higher plant phylogenetic insights for antiplasmodial drug discovery[J]. 应用天然产物, 2023, 13(5): 35-35.
[12]	Phanankosi Moyo, Luke Invernizzi, Sephora M. Mianda, Wiehan Rudolph, Andrew W. Andayi, Mingxun Wang, Neil R. Crouch, Vinesh J. Maharaj. Prioritised identification of structural classes of natural products from higher plants in the expedition of antimalarial drug discovery[J]. 应用天然产物, 2023, 13(5): 37-37.
[13]	Shah Faisal, Syed Lal Badshah, Bibi Kubra, Abdul, Hamid Emwas, and Mariusz Jaremko. Alkaloids as potential antivirals. A comprehensive review[J]. 应用天然产物, 2023, 13(1): 4-4.
[14]	Ji-Kai Liu. Natural products in cosmetics[J]. 应用天然产物, 2022, 12(6): 40-40.
[15]	Si-Yuan Luo, Jun-Yu Zhu, Ming-Feng Zou, Sheng Yin, Gui-Hua Tang. Mulberry Diels–Alder-type adducts: isolation, structure, bioactivity, and synthesis[J]. 应用天然产物, 2022, 12(5): 31-31.