Biomedical Chemistry: Research and Methods 2020, 3(2), e00127

Аnticoronaviral activity of triterpenoids

M.S. Denisov*, Ya.A. Beloglazova

Institute of Technical Chemistry of the Ural Branch of the RAS,
3 Academician Korolev str., Perm, 614013 Russia; *е-mail: denisov.m@itcras.ru

Keywords:triterpenoids; coronavirus; SARS; MERS; COVID-19

DOI:10.18097/BMCRM00127

The whole version of this paper is available in Russian.

The discovery and investigations of new therapeutic agents with anticoronaviral activity is extremely important due to the COVID-19 pandemic caused by SARS-CoV-2 virus. Currently, there is no drug against COVID-19, which efficacy has been proved in correspondence with criteria of evidence-based medicine. However, there were some precursors of SARS-CoV-2 belonging to the family Coronaviridae called SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) vuruses. Consequently, a wide range of organic substances of synthetic and natural origin were studied for the anticoronaviral activity. The review summarizes and systematizes the literature data on the anti-coronavirus activity of triterpenoids. The structural features of triterpenoids are discussed, which are important for the mechanisms of anticoronaviral activity. The structures of the most active compounds are presented. The material is classified by approaches to the study of anticoronaviral activity of individual substances or plants extracts. Recommendations for the further research of triterpenoids anticoronaviral activity are given.
Figure 1. The chemical structures of triterpenoids with tested anticoronavirus activity (compounds 1-13).
Figure 2. The chemical structures of triterpenoids with tested anticoronavirus activity (compounds 14-24, 27-31).
Figure 3. The reaction of obtaining of triterpenoid 26 from compound 25 using palladium catalysts.

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Table 1. Effects triterpenoids on coronaviruses replication at cell cultures.

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Table 2. Quantitative parameters of triterpenoids inhibiting the enzymatic activity of SARS-CoV 3CL protease.

ACKNOWLEDGEMENTS

The work was performed by the state order (project no. AAAA-A18-118030790037-7).

REFERENCES

  1. Vremenny’e metodicheskie rekomendaczii: profilaktika, diagnostika i lechenie novoj koronavirusnoj infekcii (COVID-19), Kamkin, E.G. Editor. 2020, Ministerstvo zdravooxraneniya rossijskoj federaczii, Moskow, 165 P.
    2. ' target='_blank' > DOI
  2. Ksiazek, T.G., Erdman, D., Goldsmith, C.S., Zaki, S.R., Peret, T., Emery, S., Tong, S., Urbani, C., Comer, J.A., Lim, W., Rollin, P.E., Dowell, S.F., Ling, A.E., Humphrey, C.D., Shieh, W.J., Guarner, J., Paddock, C.D., Rota, P., Fields, B., DeRisi, J., Yang, J.Y., Cox, N., Hughes, J.M., LeDuc, J.W., Bellini, W.J., Anderson, L.J. (2003) A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome. N Engl J Med., 348(20), 1953-1966. DOI
  3. Zumla, A., Hui, D.S., Perlman, S. (2015) Middle East respiratory syndrome. Lancet, 386(9997), 995-1007. DOI
  4. Nikiforov, V.V., Suranova, T.G., Chernobrovkina, T.Yu., Yankovskaya, Y.D., Burova S.V. (2020) New Coronavirus Infection (Covid-19): Clinical and Epidemiological Aspects, 10(2), 87-93. DOI
  5. Payne, S. (2017) Chapter 17 - Family Coronaviridae. Viruses, 149-158. DOI
  6. Li, Z., Tomlinson, A.C.A., Wong, A.H.M, Zhou, D., Desforges, M., Talbot, P.J., Benlekbir, S., Rubinstein, J.L., Rini, J.M. (2019) The human coronavirus HCoV-229E S-protein structure and receptor binding. Elife, 8, e51230-e51251. DOI
  7. Cheng, P.-W., Ng, L.-T., Chiang, L.-C., Lin. C.-C. (2006) Antiviral effects of saikosaponins on human coronavirus 229E in vitro. Clinical and Experimental Pharmacology and Physiology, 33(7), 612-616. DOI
  8. Arden, K.E., Nissen, M.D., Sloots, T.P., Mackay, I.M. (2005) New human coronavirus, HCoV‐NL63, associated with severe lower respiratory tract disease in Australia. Journal of medical virology, 75(3), 455-462. DOI
  9. Tsai, Y.-C., Lee, C.-L., Yen, H.-R., Chang, Y.-S., Lin, Y.-P., Huang, S.-H., Lin, C.-W. (2020) Antiviral Action of Tryptanthrin Isolated from Strobilanthes cusia Leaf against Human Coronavirus NL63 Biomolecules, 10(3), 366-373. DOI
  10. Vabret, A., Mourez, T., Gouarin, S., Petitjean, J., Freymuth, F. (2003) An Outbreak of Coronavirus OC43 Respiratory Infection in Normandy, France. Clinical infectious diseases, 36(8), 985-989. DOI
  11. Lau, S.K.P., Woo, P.C.Y., Yip, C.C.Y., Tse, H., Tsoi, H., Cheng, V.C.C., Lee, P., Tang, B.S.F., Cheung, C.H.Y., Lee, R.A., So, L., Lau, Y., Chan, K., Yuen, K. (2006) Coronavirus HKU1 and Other Coronavirus Infections in Hong Kong. J Clin Microbiol., 44(6), 2063-2071. DOI
  12. Kim, J.W., Ha, T.-K.-Q., Cho, H., Kim, E., Shim, S.H., Yang, J.-L., Oh W.K. (2017) Antiviral escin derivatives from the seeds of Aesculus turbinata Blume (Japanese horse chestnut). Bioorganic & Medicinal Chemistry Letters, 27(13), 3019-3025. DOI
  13. Baltina, L.A., Kondratenko, R.M., Baltina, L.A., Plyasunova, O.A., Pokrovskii, A.G., Tolstikov, G.A. (2009) Prospects for the creation of new antiviral drugs based on glycyrrhizic acid and its derivatives (a review). Pharmaceutical Chemistry Journal, 43(10), 539-549. DOI
  14. Kuo, R.-Y., Qian, K., Morris-Natschke, S.L., Lee, K.-H. (2009) Plant-derived triterpenoids and analogues as antitumor and anti-HIV agents. Nat. Prod. Rep., 26(10), 1321-1344. DOI
  15. Osbourn, A., Goss, R.J.M., Field, R.A. (2011) The saponins – polar isoprenoids with important and diverse biological activities Nat. Prod. Rep., 28(7), 1261-1268. DOI
  16. Shang, X., Pan, H., Li, M., Miao, X., Ding, H. (2011) Lonicera japonica Thunb.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine. Journal of Ethnopharmacology, 138(1), 1-21. DOI
  17. Gupta, S., Pandotra, P., Gupta, A.P., Verma, M.K., Ahuja, A., Vishwakarma, R.A. (2013) Direct rhizogenesis, in vitro stolon proliferation and high-throughput regeneration of plantlets in Glycyrrhiza glabra. Acta Physiol Plant, 35, 2699-2705. DOI
  18. Xiao, S., Tian, Z., Wang, Y., Si, L., Zhang, L., Zhou, D. (2018) Recent progress in the antiviral activity andmechanism study of pentacyclic triterpenoids and their derivatives. Med Res Rev, 38(3), 951-976. DOI
  19. Xiaojiaoyang, L., Xiaoyu, L., Nanaa, H., Runping, L., Rong, S. (2018) A comprehensive review and perspectives on pharmacology and toxicology of saikosaponins. Phytomedicine, 50, 73-78. DOI
  20. Peng, W., Liu, Y., Hu, M., Zhang, M., Yang, J., Liang, F., Huang, Q., Wu. C. (2019) Toona sinensis: a comprehensive review on its traditional usages, phytochemisty, pharmacology and toxicology. Revista Brasileira de Farmacognosia, 29, 111-124. DOI
  21. Batiha, G.E.-S., Beshbishy, A.M., El-Mleeh, A., Abdel-Daim, M.M., Devkota H.P. (2020) Traditional Uses, Bioactive Chemical Constituents, and Pharmacological and Toxicological Activities of Glycyrrhiza glabra L. (Fabaceae). Biomolecules, 10, 352-371. DOI
  22. Barnard, D.L., Kumaki, Y. (2011) Recent developments in anti-severe acute respiratory syndrome coronavirus chemotherapy. Future Virol., 6(5), 615-631. DOI
  23. Retrieved May 2, 2020, from: https://www.rlsnet.ru/mnn_index_id_2448.htm
  24. Cinatl, J., Morgenstern, B., Bauer, G., Chandra, P., Rabenau, H., Doerr, H.W. (2003) Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet, 361, 2045-2046. DOI
  25. Chen, H., Du, Q. (2020) Potential natural compounds for preventing 2019-nCoV infection. Preprints, 2020010358. DOI
  26. Xu, X., Chen, P., Wang, J., Feng, J., Zhou, H., Li, X., Zhong, W., Hao, P. (2020) Evolution of the Novel Coronavirus From the Ongoing Wuhan Outbreak and Modeling of Its Spike Protein for Risk of Human Transmission. Sci China Life Sci., 63(3), 457-460. DOI
  27. Wan, Y., Shang, J., Graham, R., Baric, R.S., Li, F. (2020) Receptor Recognition by the Novel Coronavirus from Wuhan: an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol., 94(7), e00127-e00136. DOI
  28. Luo Liu, P.D., Li., J. (2020) Pharmacological perspective: glycyrrhizin may be an efficacious therapeutic agent for COVID-19. International Journal of Antimicrobial Agents, in press 105995. DOI
  29. Hoever, G., Baltina, L., Michaelis, M., Kondratenko, R., Baltina, L., Tolstikov, G.A., Doerr, H.W. J. Cinatl. (2005) Antiviral Activity of Glycyrrhizic Acid Derivatives against SARS-Coronavirus. J. Med. Chem., 48, 1256-1259. DOI
  30. Baltina, L.A. (2003) Chemical Modification of Glycyrrhizic Acid As A Route to New Bioactive Compounds for Medicine. Current Medicinal Chemistry, 10, 155-171. DOI
  31. Yakovishin, L.A., Grishkovets, V.I. (2018) Molecular complexes of IVy triterpene glycosides with cholesterol. Chemistry of plant raw material, (4), 133-140. DOI
  32. Wu, C.-Y., Jan, J.-T., Ma, S.-H., Kuo, C.-J., Juan, H.-F., Cheng, Y.-S.E., Hsu, H.-H., Huang, H.-C., Wu, D., Brik, A., Liang, F.-S., Liu, R.-S., Fang, J.-M., Chen, S.-T., Liang, P.-H., Wong C.-H. (2004) Small molecules targeting severe acute respiratory syndrome human coronavirus. PNAS, 101(27), 10012-10017. DOI
  33. Petukhova, S.A., Olennikov, D.N., Mirovich, V.M. (2019) Triterpene compounds of the above ground organs of the bupleurum scorzonerifolium willd. Of the baikal region flora, (4), 215-222. DOI
  34. Wei, Y., Ma, C.-M., Hattori, M. (2009) Synthesis and Evaluation of A-seco Type Triterpenoids for anti-HIV-1protease Activity. Eur. J. Med. Chem., 44(10), 4112-4120. DOI
  35. Skvortsov, V.S., Druzhilovskiy, D.S., Veselovsky, A.V. (2020) Potential Inhibitors of Protease 3CLpro Virus COVID-19: Drug Reposition. Biomedical Chemistry: Research and Methods, 3(1), e00124-e00131. DOI
  36. Wen, C.-C., Kuo, Y.-H., Jan, J.-T., Liang, P.-H., Wang, S.-Y., Liu, H.-G., Lee, C.-K., Chang, X.S.-T., Kuo, C.-J., Lee, S.-S., Hou, C.-C., Hsiao, P.-W., Chien, S.-C., Shyur, L.-F., Yang, N.-S. (2007) Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus. J. Med. Chem., 50, 4087-4095. DOI
  37. Hsu, M.F., Kuo, C.J., Chang, K.T., Chang, H.C., Chou, C.C., Ko, T.P., Shr, H.L., Chang, G.G., Wang, A.H., Liang, P.H. (2005) Mechanism of the Maturation Process of SARS-CoV 3CL Protease. Journal of Biological Chemistry, 280(35), 31257-31266. DOI
  38. Bureeva, S., Andia-Pravdivy, J., Symon, A., Bichucher, A., Moskaleva, V., Popenko, V., Shpak, A., Shvets, V., Kozlov, L., Kaplun, A. (2007) Selective inhibition of the interaction of C1q with immunoglobulins and the classical pathway of complement activation by steroids and triterpenoids sulfates. Bioorganic & Medicinal Chemistry, 15, 3489-3498. DOI
  39. Baglivo, M., Baronio, M., Natalini, G., Beccari, T., Chiurazzi, P., Fulcheri, E., Petralia, P., Michelini, S., Fiorentini, G., Miggiano, G.A., Morresi, A., Tonini, G., Bertelli, M. (2020) Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity? Acta Biomed, 91(1), 161-164. DOI
  40. Verma, S.P. (2009) HIV: A Raft-Targeting Approach for Prevention and Therapy Using Plant-Derived Compounds (Review). Curr Drug Targets, 10(1), 51-59. DOI
  41. Rezanka, T., Siristova, L., Sigler, K. (2009) Sterols and Triterpenoids with Antiviral Activity. Anti-Infective Agents in Medicinal Chemistry, 8(3), 193-210. DOI
  42. Chang, F.-R., Yen, C.-T., EI-Shazly, M., Lin, W.-H., Yen, M.-H., Lind, K.-H., Wu, Y.-C. (2012) Anti-Human Coronavirus (anti-HCoV) Triterpenoids from the Leaves of Euphorbia neriifolia. Natural Product Communications, 7(11), 1415-1417.
  43. Yang, J.-L., Ha, T.-K.-Q., Dhodary, B., Pyo, E., Nguyen, N.H., Cho, H., Kim, E., Oh, W.K. (2015) Oleanane Triterpenes from the Flowers of Camellia japonica Inhibit Porcine Epidemic Diarrhea Virus (PEDV) Replication. J Med Chem., 58(3), 1268-1280. DOI
  44. Yang, J.-L., Ha, T.K.Q., Oh, W.K. (2016) Discovery of inhibitory materials against PEDV corona virus from medicinal plants. Japanese Journal of Veterinary Research, 64(1), 53-63. DOI
  45. Ryu, Y.B., Park, S.-J., Kim, Y.M., Lee, J.-Y., Seo, W.D., Chang, J.S., Park, K.H., Rho, M.-C., Lee, W.S. (2010) SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii. Bioorganic & Medicinal Chemistry Letters, 20(6), 1873-1876. DOI
  46. Tolkachev, O.N., Tolkachev, V.N., Sheichenko, O.P., Fateeva, T.V., Semenov, A.V., Abizov, E.A. (2018) Indole alkaloids and their analogues: biological activity study. Problems of biological, medical and pharmaceutical chemistry, (9), 3-14. DOI
  47. Lu, Y., Zhou, J., Hu, T., Zhang, Y., Su, P., Wang, J., Gao, W., Huang, L. (2018) A multifunctional oxidosqualene cyclase from Tripterygium regelii that produces both a- and bamyrin. RSC Adv., 8, 23516-23521. DOI
  48. Chen, C.-J., Michaelis, M., Hsu, H.-K., Tsai, C.-C., Yang, K.D., Wu, Y.-C., Cinatl, J., Doerrc, H.W. (2008) Toona sinensis Roem tender leaf extract inhibits SARScoronavirus replication. Journal of Ethnopharmacology, 120, 108-111. DOI