Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Antiviral Potential of the Genus Panax: An updated review on their effects and underlying mechanism of action

  • Yibo, Zhang (School of Pharmacy, Shanghai University of Traditional Chinese Medicine) ;
  • Xuanlei, Zhong (School of Pharmacy, Shanghai University of Traditional Chinese Medicine) ;
  • Zhichao, Xi (School of Pharmacy, Shanghai University of Traditional Chinese Medicine) ;
  • Yang, Li (School of Pharmacy, Shanghai University of Traditional Chinese Medicine) ;
  • Hongxi, Xu (Shuguang Hospital, Shanghai University of Traditional Chinese Medicine)
  • Received : 2022.07.04
  • Accepted : 2022.11.03
  • Published : 2023.03.02
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Abstract

Viral infections are known as one of the major factors causing death. Ginseng is a medicinal plant that demonstrated a wide range of antiviral potential, and saponins are the major bioactive ingredients in the genus Panax with vast therapeutic potential. Studies focusing on the antiviral activity of the genus Panax plant-derived agents (extracts and saponins) and their mechanisms were identified and summarized, including contributions mainly from January 2016 until January 2022. P. ginseng, P. notoginseng, and P. quinquefolius were included in the review as valuable medicinal herbs against infections with 14 types of viruses. Reports from 9 extracts and 12 bioactive saponins were included, with 6 types of protopanaxadiol (PPD) ginsenosides and 6 types of protopanaxatriol (PPT) ginsenosides. The mechanisms mainly involved the inhibition of viral attachment and replication, the modulation of immune response by regulating signaling pathways, including the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway, cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway, phosphoinositide-dependent kinase-1 (PDK1)/ protein kinase B (Akt) signaling pathway, c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) pathway, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. This review includes detailed information about the mentioned antiviral effects of the genus Panax extracts and saponins in vitro and in vivo, and in human clinical trials, which provides a scientific basis for ginseng as an adjunctive therapeutic drug or nutraceutical.

Keywords

Acknowledgement

This work was financially supported by the National Natural Science Foundation of China (No. 82204437), Shanghai Municipality Science and Technology Commission (No.22YF1445100), and Key-Area Research and DevelopmentProgram of Guangdong Province (No. 2020B1111110003).

References

  1. Pecora F, Persico F, Argentiero A, Neglia C, Esposito S. The role of micronutrients in support of the immune response against viral infections. Nutrients 2020;12(10).
  2. Zhang C, Lu LF, Li ZC, Zhou XY, Zhou Y, Chen DD, Li S, Zhang YA. Grass carp reovirus VP56 represses interferon production by degrading phosphorylated IRF7. Fish Shellfish Immunol 2020;99:99-106. https://doi.org/10.1016/j.fsi.2020.02.004
  3. Lundstrom K. Self-amplifying RNA viruses as RNA vaccines. Int J Mol Sci 2020;21(14).
  4. Lampejo T. Influenza and antiviral resistance: an overview. Eur J Clin Microbiol Infect Dis 2020;39(7):1201-8. https://doi.org/10.1007/s10096-020-03840-9
  5. Park SE, Na CS, Yoo SA, Seo SH, Son HS. Biotransformation of major ginsenosides in ginsenoside model culture by lactic acid bacteria. J Ginseng Res 2017;41(1):36-42. https://doi.org/10.1016/j.jgr.2015.12.008
  6. Mohanan P, Subramaniyam S, Mathiyalagan R, Yang DC. Molecular signaling of ginsenosides Rb1, Rg1, and Rg3 and their mode of actions. J Ginseng Res 2018;42(2):123-32. https://doi.org/10.1016/j.jgr.2017.01.008
  7. Bai L, Gao J, Wei F, Zhao J, Wang D, Wei J. Therapeutic potential of ginsenosides as an adjuvant treatment for diabetes. Front Pharmacol 2018;9:423.
  8. Liu H, Lu X, Hu Y, Fan X. Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy. Pharmacol Res 2020;161:105263.
  9. Szczuka D, Nowak A, Zaklos-Szyda M, Kochan E, Szymanska G, Motyl I, Blasiak J. American ginseng (Panax quinquefolium L.) as a source of bioactive phytochemicals with pro-health properties. Nutrients 2019;11(5).
  10. Piao XM, Huo Y, Kang JP, Mathiyalagan R, Zhang H, Yang DU, Kim M, Yang DC, Kang SC, Wang YP. Diversity of ginsenoside profiles produced by various processing technologies. Molecules 2020;25(19).
  11. Nguyen NH, Nguyen CT. Pharmacological effects of ginseng on infectious diseases. Inflammopharmacology 2019;27(5):871-83. https://doi.org/10.1007/s10787-019-00630-4
  12. Zhang T, Zhong S, Hou L, Wang Y, Xing X, Guan T, Zhang J, Li T. Computational and experimental characterization of estrogenic activities of 20(S, R)-protopanaxadiol and 20(S, R)-protopanaxatriol. J Ginseng Res 2020;44(5):690-6. https://doi.org/10.1016/j.jgr.2018.05.001
  13. Shin BK, Kwon SW, Park JH. Chemical diversity of ginseng saponins from Panax ginseng. J Ginseng Res 2015;39(4):287-98. https://doi.org/10.1016/j.jgr.2014.12.005
  14. Wensvoort G, Terpstra C, Pol JM, ter Laak EA, Bloemraad M, de Kluyver EP, Kragten C, van Buiten L, den Besten A, Wagenaar F, et al. Mystery swine disease in The Netherlands: the isolation of Lelystad virus. Vet Q 1991;13(3):121-30. https://doi.org/10.1080/01652176.1991.9694296
  15. Du T, Nan Y, Xiao S, Zhao Q, Zhou EM. Antiviral strategies against PRRSV infection. Trends Microbiol 2017;25(12):968-79. https://doi.org/10.1016/j.tim.2017.06.001
  16. Kappes MA, Faaberg KS. PRRSV structure, replication and recombination: origin of phenotype and genotype diversity. Virology 2015;479-480:475-86. https://doi.org/10.1016/j.virol.2015.02.012
  17. Lunney JK, Fang Y, Ladinig A, Chen N, Li Y, Rowland B, Renukaradhya GJ. Porcine reproductive and respiratory syndrome virus (PRRSV): pathogenesis and interaction with the immune system. Annu Rev Anim Biosci 2016;4:129-54. https://doi.org/10.1146/annurev-animal-022114-111025
  18. Yu ZQ, Yi HY, Ma J, Wei YF, Cai MK, Li Q, Qin CX, Chen YJ, Han XL, Zhong RT, et al. Ginsenoside Rg1 suppresses type 2 PRRSV infection via NF-kappaB signaling pathway in vitro, and provides partial protection against HP-PRRSV in piglet. Viruses 2019;11(11).
  19. Hu Y, Zhang B, Wang W, Zhou J, Li B, He K. Therapeutic effects of saponin components on porcine reproductive and respiratory syndrome virusinfected piglets. J Anim Physiol Anim Nutr (Berl). 2020;104(2):637-44. https://doi.org/10.1111/jpn.13302
  20. Webster RG, Bean WJ, Gorman OT, Chambers TM, Kawaoka Y. Evolution and ecology of influenza A viruses. Microbiol Rev 1992;56(1):152-79. https://doi.org/10.1128/mr.56.1.152-179.1992
  21. Takashita E, Ichikawa M, Morita H, Ogawa R, Fujisaki S, Shirakura M, Miura H, Nakamura K, Kishida N, Kuwahara T, et al. Human-to-Human transmission of influenza A(H3N2) virus with reduced susceptibility to baloxavir, Japan, february 2019. Emerg Infect Dis 2019;25(11):2108-11. https://doi.org/10.3201/eid2511.190757
  22. Joseph U, Su YC, Vijaykrishna D, Smith GJ. The ecology and adaptive evolution of influenza A interspecies transmission. Influenza Other Respir Viruses 2017;11(1):74-84. https://doi.org/10.1111/irv.12412
  23. Dong W, Farooqui A, Leon AJ, Kelvin DJ. Inhibition of influenza A virus infection by ginsenosides. PLoS One 2017;12(2):e0171936.
  24. Choi JG, Jin YH, Lee H, Oh TW, Yim NH, Cho WK, Ma JY. Protective effect of Panax notoginseng root water extract against influenza A virus infection by enhancing antiviral interferon-mediated immune responses and natural killer cell activity. Front Immunol 2017;8:1542.
  25. Kwon EB, Oh YC, Hwang YH, Li W, Park SM, Kong R, Kim YS, Choi JG. A herbal mixture formula of OCD20015-V009 prophylactic administration to enhance interferon-mediated antiviral activity against influenza A virus. Front Pharmacol 2021;12:764297.
  26. Wang Y, Jung YJ, Kim KH, Kwon Y, Kim YJ, Zhang Z, Kang HS, Wang BZ, Quan FS, Kang SM. Antiviral activity of fermented ginseng extracts against a broad range of influenza viruses. Viruses 2018;10(9).
  27. Park EH, Yum J, Ku KB, Kim HM, Kang YM, Kim JC, Kim JA, Kang YK, Seo SH. Red Ginseng-containing diet helps to protect mice and ferrets from the lethal infection by highly pathogenic H5N1 influenza virus. J Ginseng Res 2014;38(1):40-6. https://doi.org/10.1016/j.jgr.2013.11.012
  28. Kim EH, Kim SW, Park SJ, Kim S, Yu KM, Kim SG, Lee SH, Seo YK, Cho NH, Kang K, et al. Greater efficacy of black ginseng (cj EnerG) over red ginseng against lethal influenza A virus infection. Nutrients 2019;11(8).
  29. Kim H, Jang M, Kim Y, Choi J, Jeon J, Kim J, Hwang YI, Kang JS, Lee WJ. Red ginseng and vitamin C increase immune cell activity and decrease lung inflammation induced by influenza A virus/H1N1 infection. J Pharm Pharmacol 2016;68(3):406-20. https://doi.org/10.1111/jphp.12529
  30. Sreekanth TVM, Nagajyothi PC, Muthuraman P, Enkhtaivan G, Vattikuti SVP, Tettey CO, Kim DH, Shim J, Yoo K. Ultra-sonication-assisted silver nanoparticles using Panax ginseng root extract and their anti-cancer and antiviral activities. J Photochem Photobiol B 2018;188:6-11. https://doi.org/10.1016/j.jphotobiol.2018.08.013
  31. McElhaney JE, Gravenstein S, Cole SK, Davidson E, O'Neill D, Petitjean S, Rumble B, Shan JJ. A placebo-controlled trial of a proprietary extract of North American ginseng (CVT-E002) to prevent acute respiratory illness in institutionalized older adults. J Am Geriatr Soc 2004;52(1):13-9. https://doi.org/10.1111/j.1532-5415.2004.52004.x
  32. Sung H, Jung YS, Kang MW, Bae IG, Chang HH, Woo JH, Cho YK. High frequency of drug resistance mutations in human immunodeficiency virus type 1-infected Korean patients treated with HAART. AIDS Res Hum Retroviruses 2007;23(10):1223-9. https://doi.org/10.1089/aid.2007.0008
  33. Lu DY, Wu HY, Yarla NS, Xu B, Ding J, Lu TR. HAART in HIV/AIDS treatments: future trends. Infect Disord Drug Targets 2018;18(1):15-22. https://doi.org/10.2174/1871526517666170505122800
  34. 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(2):222-6. https://doi.org/10.1016/j.jgr.2016.12.006
  35. 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(4):497-501. https://doi.org/10.1128/CDLI.12.4.497-501.2005
  36. Sung H, Jung YS, Cho YK. Beneficial effects of a combination of Korean red ginseng and highly active antiretroviral therapy in human immunodeficiency virus type 1-infected patients. Clin Vaccine Immunol 2009;16(8):1127-31. https://doi.org/10.1128/CVI.00013-09
  37. Cho YK, Kim JE. The frequency of defective genes in vif and vpr genes in 20 hemophiliacs is associated with Korean Red Ginseng and highly active antiretroviral therapy: the impact of lethal mutations in vif and vpr genes on HIV-1 evolution. J Ginseng Res 2021;45(1):149-55. https://doi.org/10.1016/j.jgr.2020.03.003
  38. Cho YK, Kim JE, Woo JH. Korean Red Ginseng increases defective pol gene in peripheral blood mononuclear cells of HIV-1-infected patients; inhibition of its detection during ginseng-based combination therapy. J Ginseng Res 2019;43(4):684-91. https://doi.org/10.1016/j.jgr.2019.05.011
  39. Baggen J, Thibaut HJ, Strating J, van Kuppeveld FJM. The life cycle of non-polio enteroviruses and how to target it. Nat Rev Microbiol 2018;16(6):368-81. https://doi.org/10.1038/s41579-018-0005-4
  40. Khanna M, Gautam A, Rajput R, Sharma L. Natural products as a paradigm for the treatment of coxsackievirus - induced myocarditis. Curr Top Med Chem 2020;20(8):607-16. https://doi.org/10.2174/1568026620666200129094516
  41. Pan L, Zhang Y, Lu J, Geng Z, Jia L, Rong X, Wang Z, Zhao Q, Wu R, Chu M, et al. Panax notoginseng saponins ameliorates coxsackievirus B3-induced myocarditis by activating the cystathionine-gamma-lyase/hydrogen sulfide pathway. J Cardiovasc Transl Res 2015;8(9):536-44. https://doi.org/10.1007/s12265-015-9659-8
  42. Wang X, Wang Y, Ren Z, Qian C, Li Y, Wang Q, Zhang Y, Zheng L, Jiang J, Yang C, et al. Protective effects of 20(s)-protopanaxtriol on viral myocarditis infected by coxsackievirus B3. Pathobiology 2012;79(6):285-9. https://doi.org/10.1159/000331229
  43. Ventarola D, Bordone L, Silverberg N. Update on hand-foot-and-mouth disease. Clin Dermatol 2015;33(3):340-6. https://doi.org/10.1016/j.clindermatol.2014.12.011
  44. You L, Chen J, Liu W, Xiang Q, Luo Z, Wang W, Xu W, Wu K, Zhang Q, Liu Y, et al. Enterovirus 71 induces neural cell apoptosis and autophagy through promoting ACOX1 downregulation and ROS generation. Virulence 2020;11(1):537-53. https://doi.org/10.1080/21505594.2020.1766790
  45. Kang N, Gao H, He L, Liu Y, Fan H, Xu Q, Yang S. Ginsenoside Rb1 is an immune-stimulatory agent with antiviral activity against enterovirus 71. J Ethnopharmacol 2021;266:113401.
  46. 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(3):173-9. https://doi.org/10.1016/j.jgr.2014.04.003
  47. Bergroth E, Aakula M, Elenius V, Remes S, Piippo-Savolainen E, Korppi M, Piedra PA, Bochkov YA, Gern JE, Camargo Jr CA, et al. Rhinovirus type in severe bronchiolitis and the development of asthma. J Allergy Clin Immunol Pract 2020;8(2):588-595 e4.
  48. Makris S, Johnston S. Recent advances in understanding rhinovirus immunity. F1000Res 2018;7.
  49. Fukushima A, Yoo YC, Yoshimatsu K, Matsuzawa K, Tamura M, Tono-oka S, Taniguchi K, Urasawa S, Arikawa J, Azuma I. Effect of MDP-Lys(L18) as a mucosal immunoadjuvant on protection of mucosal infections by Sendai virus and rotavirus. Vaccine 1996;14(6):485-91. https://doi.org/10.1016/0264-410X(95)00236-T
  50. Yoo YC, Lee J, Park SR, Nam KY, Cho YH, Choi JE. Protective effect of ginsenoside-Rb2 from Korean red ginseng on the lethal infection of haemagglutinating virus of Japan in mice. J Ginseng Res 2013;37(1):80-6. https://doi.org/10.5142/jgr.2013.37.80
  51. Sadiq A, Bostan N, Yinda KC, Naseem S, Sattar S. Rotavirus: genetics, pathogenesis and vaccine advances. Rev Med Virol 2018;28(6):e2003.
  52. Mortality GBD. Causes of Death C. Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet 2016;388:1459-544. 10053. https://doi.org/10.1016/S0140-6736(16)31012-1
  53. Yang H, Oh KH, Kim HJ, Cho YH, Yoo YC. Ginsenoside-Rb2 and 20(S)-Ginsenoside-Rg3 from Korean red ginseng prevent rotavirus infection in newborn mice. J Microbiol Biotechnol 2018;28(3):391-6. https://doi.org/10.4014/jmb.1801.01006
  54. Connolly SA, Jardetzky TS, Longnecker R. The structural basis of herpesvirus entry. Nat Rev Microbiol 2021;19(2):110-21. https://doi.org/10.1038/s41579-020-00448-w
  55. Dadwal SS. Herpes virus infections other than cytomegalovirus in the recipients of hematopoietic stem cell transplantation. Infect Dis Clin North Am 2019;33(2):467-84. https://doi.org/10.1016/j.idc.2019.02.012
  56. Simas JP, Efstathiou S. Murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis. Trends Microbiol 1998;6(7):276-82. https://doi.org/10.1016/S0966-842X(98)01306-7
  57. Aligo J, Walker M, Bugelski P, Weinstock D. Is murine gammaherpesvirus-68 (MHV-68) a suitable immunotoxicological model for examining immunomodulatory drug-associated viral recrudescence? J Immunotoxicol 2015;12(1):1-15. https://doi.org/10.3109/1547691X.2014.882996
  58. Manners O, Murphy JC, Coleman A, Hughes DJ, Whitehouse A. Contribution of the KSHV and EBV lytic cycles to tumourigenesis. Curr Opin Virol 2018;32:60-70. https://doi.org/10.1016/j.coviro.2018.08.014
  59. Kang S, Im K, Kim G, Min H. Antiviral activity of 20(R)-ginsenoside Rh2 against murine gammaherpesvirus. J Ginseng Res 2017;41(4):496-502. https://doi.org/10.1016/j.jgr.2016.08.010
  60. Wright S, Altman E. Inhibition of herpes simplex viruses, types 1 and 2, by ginsenoside 20(S)-Rg3. J Microbiol Biotechnol 2020;30(1):101-8. https://doi.org/10.4014/jmb.1908.08047
  61. Kang S, Song MJ, Min H. Antiviral activity of ginsenoside Rg3 isomers against gammaherpesvirus through inhibition of p38- and JNK-associated pathways. Journal of Functional Foods 2018;40:219-28. https://doi.org/10.1016/j.jff.2017.11.011
  62. Petti S, Lodi G. The controversial natural history of oral herpes simplex virus type 1 infection. Oral Dis 2019;25(8):1850-65. https://doi.org/10.1111/odi.13234
  63. Schiffer JT, Gottlieb SL. Biologic interactions between HSV-2 and HIV-1 and possible implications for HSV vaccine development. Vaccine 2019;37(50):7363-71. https://doi.org/10.1016/j.vaccine.2017.09.044
  64. Xu X, Zhang Y, Li Q. Characteristics of herpes simplex virus infection and pathogenesis suggest a strategy for vaccine development. Rev Med Virol 2019;29(4):e2054.
  65. Daikoku T, Tannai H, Honda M, Onoe T, Matsuo K, Onoye Y, Nishizawa M, Kawana T, Okuda T, Hasegawa T, et al. Subclinical generation of acyclovirresistant herpes simplex virus with mutation of homopolymeric guanosine strings during acyclovir therapy. J Dermatol Sci 2016;82(3):160-5. https://doi.org/10.1016/j.jdermsci.2016.02.006
  66. Anton-Vazquez V, Mehra V, Mbisa JL, Bradshaw D, Basu TN, Daly ML, Mufti GJ, Pagliuca A, Potter V, Zuckerman M. Challenges of aciclovir-resistant HSV infection in allogeneic bone marrow transplant recipients. J Clin Virol 2020;128:104421.
  67. Cho A, Roh YS, Uyangaa E, Park S, Kim JW, Lim KH, Kwon J, Eo SK, Lim CW, Kim B. Protective effects of red ginseng extract against vaginal herpes simplex virus infection. J Ginseng Res 2013;37(2):210-8. https://doi.org/10.5142/jgr.2013.37.210
  68. Heim K, Neumann-Haefelin C, Thimme R, Hofmann M. Heterogeneity of HBV-specific CD8(+) T-cell failure: implications for immunotherapy. Front Immunol 2019;10:2240.
  69. Gane EJ. Future anti-HBV strategies. Liver Int 2017;37(Suppl 1):40-4. https://doi.org/10.1111/liv.13304
  70. Choi SH, Yang KJ, Lee DS. Effects of complementary combination therapy of Korean red ginseng and antiviral agents in chronic hepatitis B. J Altern Complement Med 2016;22(12):964-9. https://doi.org/10.1089/acm.2015.0206
  71. 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(11):2612-21. https://doi.org/10.1016/j.biocel.2013.08.016
  72. Westerhoff M, Ahn J. Chronic hepatitis C and direct acting antivirals. Surg Pathol Clin 2018;11(2):287-96. https://doi.org/10.1016/j.path.2018.02.002
  73. Baumert TF, Berg T, Lim JK, Nelson DR. Status of direct-acting antiviral therapy for hepatitis C virus infection and remaining challenges. Gastroenterology 2019;156(2):431-45. https://doi.org/10.1053/j.gastro.2018.10.024
  74. Kim SJ, Syed GH, Khan M, Chiu WW, Sohail MA, Gish RG, Siddiqui A. Hepatitis C virus triggers mitochondrial fission and attenuates apoptosis to promote viral persistence. Proc Natl Acad Sci U S A 2014;111(17):6413-8. https://doi.org/10.1073/pnas.1321114111
  75. Jassey A, Liu CH, Changou CA, Richardson CD, Hsu HY, Lin LT. Hepatitis C virus non-structural protein 5A (NS5A) disrupts mitochondrial dynamics and induces mitophagy. Cells 2019;8(4).
  76. Kim SJ, Jang JY, Kim EJ, Cho EK, Ahn DG, Kim C, Park HS, Jeong SW, Lee SH, Kim SG, et al. Ginsenoside Rg3 restores hepatitis C virus-induced aberrant mitochondrial dynamics and inhibits virus propagation. Hepatology 2017;66(3):758-71. https://doi.org/10.1002/hep.29177
  77. Reshi L, Wu JL, Wang HV, Hong JR. Aquatic viruses induce host cell death pathways and its application. Virus Res 2016;211:133-44. https://doi.org/10.1016/j.virusres.2015.10.018
  78. Dai J, Zhang L, Zhang P, Shu H, Mao A, Li Y. Ginsenoside Rg3 inhibits grass carp reovirus replication in grass carp ovarian epithelial cells. Microb Pathog 2020;144:104174.
  79. Cox RM, Plemper RK. Structure and organization of paramyxovirus particles. Curr Opin Virol 2017;24:105-14. https://doi.org/10.1016/j.coviro.2017.05.004
  80. Gowthaman V, Singh SD, Dhama K, Desingu PA, Kumar A, Malik YS, Munir M. Isolation and characterization of genotype XIII Newcastle disease virus from Emu in India. Virusdisease 2016;27(3):315-8. https://doi.org/10.1007/s13337-016-0324-x
  81. Ma X, Bi S, Wang Y, Chi X, Hu S. Combined adjuvant effect of ginseng stem-leaf saponins and selenium on immune responses to a live bivalent vaccine of Newcastle disease virus and infectious bronchitis virus in chickens. Poult Sci 2019;98(9):3548-56. https://doi.org/10.3382/ps/pez207
  82. Zhai L, Li Y, Wang W, Wang Y, Hu S. Effect of oral administration of ginseng stem-and-leaf saponins (GSLS) on the immune responses to Newcastle disease vaccine in chickens. Vaccine 2011;29(31):5007-14. https://doi.org/10.1016/j.vaccine.2011.04.097
  83. Blome S, Staubach C, Henke J, Carlson J, Beer M. Classical swine fever-an updated review. Viruses 2017;9(4).
  84. Chernick A, Ambagala A, Orsel K, Wasmuth JD, van Marle G, van der Meer F. Bovine viral diarrhea virus genomic variation within persistently infected cattle. Infect Genet Evol 2018;58:218-23. https://doi.org/10.1016/j.meegid.2018.01.002
  85. Pecora A, Perez Aguirreburualde MS, Ridpath JF, Dus Santos MJ. Molecular characterization of pestiviruses in fetal bovine sera originating from Argentina: evidence of circulation of HoBi-like viruses. Front Vet Sci 2019;6:359.
  86. Tong W, Zheng H, Li GX, Gao F, Shan TL, Zhou YJ, Yu H, Jiang YF, Yu LX, Li LW, et al. Recombinant pseudorabies virus expressing E2 of classical swine fever virus (CSFV) protects against both virulent pseudorabies virus and CSFV. Antiviral Res 2020;173:104652.
  87. Tan B, Giangaspero M, Sun N, Jin Y, Liu K, Wang Q, Cheng S, Wang Y, Zhang S. Antiviral effect of ginsenoside Rb2 and Rb3 against bovine viral diarrhea virus and classical swine fever virus in vitro. Front Vet Sci 2021;8:764909.
  88. Nam HH, Ison MG. Respiratory syncytial virus infection in adults. BMJ 2019;366:l5021. https://doi.org/10.1136/bmj.l5779
  89. Shi T, McAllister DA, O'Brien KL, Simoes EAF, Madhi SA, Gessner BD, Polack FP, Balsells E, Acacio S, Aguayo C, et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet 2017;390:946-58. 10098. https://doi.org/10.1016/S0140-6736(17)30938-8
  90. Lee JS, Ko EJ, Hwang HS, Lee YN, Kwon YM, Kim MC, Kang SM. Antiviral activity of ginseng extract against respiratory syncytial virus infection. Int J Mol Med 2014;34(1):183-90. https://doi.org/10.3892/ijmm.2014.1750
  91. Lee JS, Lee YN, Lee YT, Hwang HS, Kim KH, Ko EJ, Kim MC, Kang SM. Ginseng protects against respiratory syncytial virus by modulating multiple immune cells and inhibiting viral replication. Nutrients 2015;7(2):1021-36. https://doi.org/10.3390/nu7021021
  92. Lee JS, Cho MK, Hwang HS, Ko EJ, Lee YN, Kwon YM, Kim MC, Kim KH, Lee YT, Jung YJ, et al. Ginseng diminishes lung disease in mice immunized with formalin-inactivated respiratory syncytial virus after challenge by modulating host immune responses. J Interferon Cytokine Res 2014;34(11):902-14. https://doi.org/10.1089/jir.2013.0093
  93. Vohra S, Johnston BC, Laycock KL, Midodzi WK, Dhunnoo I, Harris E, Baydala L. Safety and tolerability of North American ginseng extract in the treatment of pediatric upper respiratory tract infection: a phase II randomized, controlled trial of 2 dosing schedules. Pediatrics 2008;122(2):e402-10. https://doi.org/10.1542/peds.2007-2186
  94. Xie X, Hu L, Xue H, Xiong Y, Panayi AC, Lin Z, Chen L, Yan C, Zhou W, Mi B, et al. Prognosis and treatment of complications associated with COVID-19: a systematic review and meta-analysis. Acta Materia Medica.1(1):124-137.
  95. Yang J, Yang Y. Regulatory lessons from China's COVID-19 vaccines development and approval policies. Acta Materia Medica.1(1):96-105.
  96. Oesch F, Oesch-Bartlomowicz B, Efferth T. Toxicity as prime selection criterion among SARS-active herbal medications. Phytomedicine 2021;85:153476.
  97. Park HH, Kim H, Lee HS, Seo EU, Kim JE, Lee JH, Mun YH, Yoo SY, An J, Yun MY, et al. PEGylated nanoparticle albumin-bound steroidal ginsenoside derivatives ameliorate SARS-CoV-2-mediated hyper-inflammatory responses. Biomaterials 2021;273:120827.
  98. Sharma P, Tyagi A, Bhansali P, Pareek S, Singh V, Ilyas A, Mishra R, Poddar NK. Saponins: extraction, bio-medicinal properties and way forward to anti-viral representatives. Food Chem Toxicol 2021;150:112075.
  99. Wang C, Liu J, Deng J, Wang J, Weng W, Chu H, Meng Q. Advances in the chemistry, pharmacological diversity, and metabolism of 20(R)-ginseng saponins. J Ginseng Res 2020;44(1):14-23.  https://doi.org/10.1016/j.jgr.2019.01.005