Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Antiviral effects of Korean Red Ginseng on human coronavirus OC43

  • Chi Hwan, Jeong (College of Pharmacy, Chung-Ang University) ;
  • Jisu, Kim (College of Pharmacy, Chung-Ang University) ;
  • Bo Kyeong, Kim (College of Pharmacy, Chung-Ang University) ;
  • Kang Bin, Dan (College of Pharmacy, Chung-Ang University) ;
  • Hyeyoung, Min (College of Pharmacy, Chung-Ang University)
  • Received : 2022.08.03
  • Accepted : 2022.09.29
  • Published : 2023.03.02
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Panax ginseng Meyer is a medicinal plant well-known for its antiviral activities against various viruses, but its antiviral effect on coronavirus has not yet been studied thoroughly. The antiviral activity of Korean Red Ginseng (KRG) and ten ginsenosides against Human coronavirus OC43 (HCoV-OC43) was investigated in vitro. Methods: The antiviral response and mechanism of action of KRG extract and ginsenoside Rc, Re, Rf, Rg1, Rg2-20 (R) and -20 (S), Rg3-20 (R) and -20 (S), and Rh2-20 (R) and -20 (S), against the human coronavirus strain OC43 were investigated by using plaque assay, time of addition assay, real-time PCR, and FACS analysis. Results: Virus plaque formation was reduced in KRG extract-treated and HCoV-OC43-infected HCT-8 cells. KRG extract decreased the viral proteins (Nucleocapsid protein and Spike protein) and mRNA (N and M gene) expression, while increased the expression of interferon genes. Conclusion: KRG extract exhibits antiviral activity by enhancing the expression of interferons and can be used in treating infections caused by HCoV-OC43.

Keywords

Acknowledgement

This research was supported by the Chung-Ang University Research Scholarship Grants in 2022, and by a 2021 grant from the Korean Society of Ginseng.

References

  1. Mourya DT, Sapkal G, Yadav PD, Sk MB, Shete A, Gupta N. Biorisk assessment for infrastructure & biosafety requirements for the laboratories providing coronavirus SARS-CoV-2/(COVID-19) diagnosis. Indian J Med Res 2020;151:172-6.  https://doi.org/10.4103/ijmr.IJMR_763_20
  2. Woo PC, Huang Y, Lau SK, Yuen KY. Coronavirus genomics and bioinformatics analysis. Viruses 2010;2:1804-20.  https://doi.org/10.3390/v2081803
  3. Vijgen L, Keyaerts E, Moes E, Thoelen I, Wollants E, Lemey P, Vandamme AM, Van Ranst M. Complete genomic sequence of human coronavirus OC43: molecular clock analysis suggests a relatively recent zoonotic coronavirus transmission event. J Virol 2005;79:1595-604.  https://doi.org/10.1128/JVI.79.3.1595-1604.2005
  4. Lim YX, Ng YL, Tam JP, Liu DX. Human coronaviruses: a review of virus-host interactions. Diseases 2016;4. 
  5. Cabeca TK, Granato C, Bellei N. Epidemiological and clinical features of human coronavirus infections among different subsets of patients. Influenza Other Respir Viruses 2013;7:1040-7.  https://doi.org/10.1111/irv.12101
  6. Brown AJ, Won JJ, Graham RL, Dinnon 3rd KH, Sims AC, Feng JY, Cihlar T, Denison MR, Baric RS, Sheahan TP. Broad spectrum antiviral remdesivir inhibits human endemic and zoonotic deltacoronaviruses with a highly divergent RNA dependent RNA polymerase. Antiviral Res 2019;169:104541. 
  7. van der Hoek L. Human coronaviruses: what do they cause? Antivir Ther 2007;12:651-8.  https://doi.org/10.1177/135965350701200S01.1
  8. Yang C-W, Peng T-T, Hsu H-Y, Lee Y-Z, Wu S-H, Lin W-H, Ke Y-Y, Hsu T-A, Yeh T-K, Huang W-Z. Repurposing old drugs as antiviral agents for coronaviruses. Biomedical Journal 2020;43:368-74.  https://doi.org/10.1016/j.bj.2020.05.003
  9. Hu Y, Meng X, Zhang F, Xiang Y, Wang J. The in vitro antiviral activity of lactoferrin against common human coronaviruses and SARS-CoV-2 is mediated by targeting the heparan sulfate co-receptor. Emerg Microbes Infect 2021;10:317-30.  https://doi.org/10.1080/22221751.2021.1888660
  10. Larson HE, Reed SE, Tyrrell DA. Isolation of rhinoviruses and coronaviruses from 38 colds in adults. J Med Virol 1980;5:221-9.  https://doi.org/10.1002/jmv.1890050306
  11. Zhao X, Guo F, Liu F, Cuconati A, Chang J, Block TM, Guo JT. Interferon induction of IFITM proteins promotes infection by human coronavirus OC43. Proc Natl Acad Sci U S A 2014;111:6756-61.  https://doi.org/10.1073/pnas.1320856111
  12. Gaunt ER, Hardie A, Claas EC, Simmonds P, Templeton KE. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. J Clin Microbiol 2010;48:2940-7.  https://doi.org/10.1128/JCM.00636-10
  13. St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ. Human respiratory coronavirus OC43: genetic stability and neuroinvasion. J Virol 2004;78:8824-34.  https://doi.org/10.1128/JVI.78.16.8824-8834.2004
  14. Beidas M, Chehadeh W. PCR array profiling of antiviral genes in human embryonic kidney cells expressing human coronavirus OC43 structural and accessory proteins. Arch Virol 2018;163:2065-72.  https://doi.org/10.1007/s00705-018-3832-8
  15. Tamminen K, Salminen M, Blazevic V. Seroprevalence and SARS-CoV-2 cross-reactivity of endemic coronavirus OC43 and 229E antibodies in Finnish children and adults. Clin Immunol 2021;229:108782. 
  16. Yamaguchi T, Shinagawa T, Kobata H, Nakagawa H. Immunity against seasonal human coronavirus OC43 mitigates fatal deterioration of COVID-19. Int J Infect Dis 2021;109:261-8.  https://doi.org/10.1016/j.ijid.2021.07.015
  17. Scaglione F, Ferrara F, Dugnani S, Falchi M, Santoro G, Fraschini F. Immunomodulatory effects of two extracts of Panax ginseng C.A. Meyer. Drugs Exp Clin Res 1990;16:537-42. 
  18. See DM, Broumand N, Sahl L, Tilles JG. In vitro effects of echinacea and ginseng on natural killer and antibody-dependent cell cytotoxicity in healthy subjects and chronic fatigue syndrome or acquired immunodeficiency syndrome patients. Immunopharmacology 1997;35:229-35.  https://doi.org/10.1016/S0162-3109(96)00125-7
  19. Helms S. Cancer prevention and therapeutics: Panax ginseng. Altern Med Rev 2004;9:259-74. 
  20. Kim SK, Park JH. Trends in ginseng research in 2010. J Ginseng Res 2011;35: 389-98.  https://doi.org/10.5142/jgr.2011.35.4.389
  21. Kim S, Lee Y, Cho J. Korean red ginseng extract exhibits neuroprotective effects through inhibition of apoptotic cell death. Biol Pharm Bull 2014;37:938-46.  https://doi.org/10.1248/bpb.b13-00880
  22. Sung WS, Lee DG. The combination effect of Korean red ginseng saponins with kanamycin and cefotaxime against methicillin-resistant Staphylococcus aureus. Biol Pharm Bull 2008;31:1614-7.  https://doi.org/10.1248/bpb.31.1614
  23. Im K, Kim J, Min H. Ginseng, the natural effectual antiviral: protective effects of Korean Red Ginseng against viral infection. J Ginseng Res 2016;40:309-14.  https://doi.org/10.1016/j.jgr.2015.09.002
  24. Lee MH, Lee BH, Lee S, Choi C. Reduction of hepatitis A virus on FRhK-4 cells treated with Korean red ginseng extract and ginsenosides. J Food Sci 2013;78:M1412-5.  https://doi.org/10.1111/1750-3841.12205
  25. Sung H, Kang SM, Lee MS, Kim TG, Cho YK. Korean red ginseng slows depletion of CD4 T cells in human immunodeficiency virus type 1-infected patients. Clin Diagn Lab Immunol 2005;12:497-501.  https://doi.org/10.1128/CDLI.12.4.497-501.2005
  26. Kang S, Im K, Kim G, Min H. Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus. J Ginseng Res 2017;41:496-502.  https://doi.org/10.1016/j.jgr.2016.08.010
  27. Song JH, Choi HJ, Song HH, Hong EH, Lee BR, Oh SR, Choi K, Yeo SG, Lee YP, Cho S, et al. Antiviral activity of ginsenosides against coxsackievirus B3, enterovirus 71, and human rhinovirus 3. J Ginseng Res 2014;38:173-9.  https://doi.org/10.1016/j.jgr.2014.04.003
  28. Cho YK, Kim JE. Effect of Korean Red Ginseng intake on the survival duration of human immunodeficiency virus type 1 patients. J Ginseng Res 2017;41:222-6.  https://doi.org/10.1016/j.jgr.2016.12.006
  29. Lee MH, Lee BH, Jung JY, Cheon DS, Kim KT, Choi C. Antiviral effect of Korean red ginseng extract and ginsenosides on murine norovirus and feline calicivirus as surrogates for human norovirus. J Ginseng Res 2011;35:429-35.  https://doi.org/10.5142/jgr.2011.35.4.429
  30. Park JD, Rhee DK, Lee YH. Biological activities and chemistry of saponins from Panax ginseng CA Meyer. Phytochemistry Reviews 2005;4:159-75.  https://doi.org/10.1007/s11101-005-2835-8
  31. Kang S, Min H. Ginseng, the 'immunity boost': the effects of Panax ginseng on immune System. J Ginseng Res 2012;36:354-68.  https://doi.org/10.5142/jgr.2012.36.4.354
  32. Kang LJ, Choi YJ, Lee SG. Stimulation of TRAF6/TAK1 degradation and inhibition of JNK/AP-1 signalling by ginsenoside Rg3 attenuates hepatitis B virus replication. Int J Biochem Cell Biol 2013;45:2612-21.  https://doi.org/10.1016/j.biocel.2013.08.016
  33. Lee MH, Seo DJ, Kang JH, Oh SH, Choi C. Expression of antiviral cytokines in Crandell-Reese feline kidney cells pretreated with Korean red ginseng extract or ginsenosides. Food Chem Toxicol 2014;70:19-25.  https://doi.org/10.1016/j.fct.2014.04.034
  34. Liang YY, Wang B, Qian DM, Li L, Wang ZH, Hu M, Song XX. Inhibitory effects of Ginsenoside Rb1 on apoptosis caused by HSV-1 in human glioma cells. Virol Sin 2012;27:19-25.  https://doi.org/10.1007/s12250-012-3220-6
  35. Wu CY, Jan JT, Ma SH, Kuo CJ, Juan HF, Cheng YS, Hsu HH, Huang HC, Wu D, Brik A, et al. Small molecules targeting severe acute respiratory syndrome human coronavirus. Proc Natl Acad Sci U S A 2004;101:10012-7.  https://doi.org/10.1073/pnas.0403596101
  36. Parker MM, Masters PS. Sequence comparison of the N genes of five strains of the coronavirus mouse hepatitis virus suggests a three domain structure for the nucleocapsid protein. Virology 1990;179:463-8.  https://doi.org/10.1016/0042-6822(90)90316-J
  37. Kuo L, Masters PS. Genetic evidence for a structural interaction between the carboxy termini of the membrane and nucleocapsid proteins of mouse hepatitis virus. J Virol 2002;76:4987-99.  https://doi.org/10.1128/JVI.76.10.4987-4999.2002
  38. Samuel CE. Antiviral actions of interferons. Clin Microbiol Rev 2001;14: 778e809. table of contents. 
  39. McNab F, Mayer-Barber K, Sher A, Wack A, O'Garra A. Type I interferons in infectious disease. Nat Rev Immunol 2015;15:87-103.  https://doi.org/10.1038/nri3787
  40. Fritsch SD, Weichhart T. Effects of interferons and viruses on metabolism. Front Immunol 2016;7:630. 
  41. Beidas M, Chehadeh W. Effect of human coronavirus OC43 structural and accessory proteins on the transcriptional activation of antiviral response elements. Intervirology 2018;61:30-5.  https://doi.org/10.1159/000490566
  42. Hyun SH, Kim SW, Seo HW, Youn SH, Kyung JS, Lee YY, In G, Park CK, Han CK. Physiological and pharmacological features of the non-saponin components in Korean Red Ginseng. J Ginseng Res 2020;44:527-37. https://doi.org/10.1016/j.jgr.2020.01.005