The Possible Effects of Asiatic Herbs in SARS-COV-2 and their Mechanism of Action

Ferro M.*, Graubard A., Ledezma R., Escalante P., Channan G., Dotres V. and Bencomo Y.

Department of Sciences, Nutrition Formulators Inc., Miramar, Fl, USA.

In 2019, a new virus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) gave rise to an unknown outbreak that spread in China’s Hubei province, triggering a new epidemic
known as coronavirus-19 (COVID -19). Several studies have demonstrated the metabolic pathways of SARS-COV-2 in angiotensin-converting enzyme receptors 2 (ACE2). With this, others have been considering an approach with drugs that bind to ACE2 receptors as well as antiviral activity as a possible treatment option for the disease. Thus, the objective of this present review was to evaluate some Asiatic herbs for both the prevention and treatment of COVID-19. Some herbs, such as the extract of Artemisia annua (Artemisinins) and the extract of Isatis
indigotica (Emodin), showed to be effective as inhibitors of adhesion of some viruses. Some studies observed this in the SARS-CoV S / ACE -2 protein interaction in which it inhibited the adhesion of the virus to the cell surface. Similarly, Glycyrrhiza glabra extract (Licorice) showed significant inhibiting action on the influenza virus and was shown to be an effective antiviral in many other viruses by weakening virus activity, such as inhibiting virus gene expression and replication, reducing adhesion force and stress through the reduction of high-mobility-group box1 (HMGB1) binding to DNA. Additionally, one of the best herbs in effective concentration value (EC50) found in this study was Lycoris Radiata with EC50: 2,4 ± 0.2 μg / ml. The results presented in this review are promising in the search for prophylactic treatment in a viral pandemic such as SARS-VOC-2. However, more clinical trials to validate the processes of the effectiveness of both plants and their extracts, as well as the synergy between the plants themselves are needed to validate future herbal treatments against SARS-VOC-2.

Keywords: SARS-COV-2; ACE2; COVID-19; Asiatic Herbs

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How to cite this article:
Ferro M., Graubard A., Ledezma R., Escalante P., Channan G., Dotres V. and Bencomo Y.. The Possible Effects of Asiatic Herbs in SARS-COV-2 and their Mechanism of Action. American Journal of Anatomy and Physiology, 2021; 4:15. DOI:10.28933/ajap-2020-12-0305


1. Esakandari H, Nabi-afjadi M, Fakkari-afjadi J, Farahmandian N, Miresmaeili S, Bahrein E. A comprehensive review of COVID-19 characteristics. Biol Proced Online. 2020; 22: 19.
2. Yuen KS, Ye Z.W, Fung SY, Chan CP, Jin DY. SARS-CoV-2 and COVID-19: The most important research questions. Cell Biosci. 2020; 10():40.
3. Zabetakis I, Lordan R., Norton C., Tsoupras A. COVID-19: The Inflammation Link and the Role of Nutrition in Potential Mitigation. Nutrients 2020, 12(5), 1466.
4. Ioannidis JPA, Axfors C, Contopoulos-Ioannidis DG. Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters. Environ Res. 2020 Sep; 188: 109890.
5. Gelman R, Bayatra A, Kessler A, Schwartz A, Ilan Y. Targeting SARS-CoV-2 receptors as a means for reducing infectivity and improving antiviral and immune response: an algorithm-based method for overcoming resistance to antiviral agents. Emerg Microbes Infect. 2020; 9(1): 1397– 1406.
6. Zhou D, Duyvesteyn HME, Huang KA. Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient. Nature Structural & Molecular Biology (2020).
7. Sever P and Johnston SL. The Renin-Angiotensin system and SARS-CoV-2 infection: A role for the ACE2 receptor? Journal of the Renin-AngiotensinAldosterone System. April-June 2020: 1–2.
8. Turner AJ, Hiscox JA and Hooper NM. ACE2: from vasopeptidase to SARS virus receptor. TRENDS in Pharmacological Sciences Vol.25 No.6 June 2004
9. Banua N, Panikarb SS, Lealc LR, Leald AR. Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to Macrophage Activation Syndrome: Therapeutic implications. Life Sciences. Volume 256, 1 September 2020, 117905.
10. Garg S, Kim L, Whitaker M, O’Halloran A, Cummings C, et al. Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 — COVID-NET, 14 States, March 1–30, 2020. Weekly / April 17, 2020 / 69(15);458–464.
11. Ziegler CGK, Allon SJ, Nyquist SK, Mbano IM, Vincent N Miao VN, et al. SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues. Cell. 2020 May 28;181(5):1016-1035.e19.
12. Satarker S, Nampoothiri M. Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2. Archives of Medical Research Volume 51, Issue 6, August 2020, Pages 482-491.
13. Wu XD, Shang B, Yang RF, Yu H, Ma ZH, et al. The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells. Cell Research volume 14, pages400– 406(2004).
14. Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T. et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020 Apr 16;181(2):271-280.e8.
15. Li W, Moore MJ, Vasilieva N, Sui J, Wong SK, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature volume 426, pages450–454(2003).
16. Hamilton BS, Gludish DWJ, Whittake GR. Cleavage Activation of the Human-Adapted Influenza Virus Subtypes by Matriptase Reveals both Subtype and Strain Specificities. J Virol. 2012 Oct; 86(19): 10579–10586.
17. Munster VJ, Feldmann F, Williamson BN, van Doremalen N, Pérez-Pérez L, et al. Respiratory disease in rhesus macaques inoculated with SARS-CoV-2. Nature volume 585, pages268– 272(2020).
18. Ding Y, He L, Zhang Q, Huang Z, Che X, et al. Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways. J Pathol. 2004 Jun;203(2):622-30.
19. Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004 Jun;203(2):631-7.
20. Cheong DHJ, Tan DWS, Wong FWS, Tran T. Anti-malarial drug, artemisinin and its derivatives for the treatment of respiratory diseases. Pharmacol Res. 2020 Aug;158:104901.
21. Sharifkashani S, Bafrani MA, Khaboushan AS, Pirzadeh M, Kheirandish A, et al. Angiotensinconverting enzyme 2 (ACE2) receptor and SARS-CoV-2: Potential therapeutic targeting. European Journal of Pharmacology. Volume 884, 5 October 2020, 173455.
22. Li Q, Wang H, Li X, Zheng Y, Wei Y, et al. The role played by traditional Chinese medicine in preventing and treating COVID-19 in China. Frontiers of Medicine (2020).
23. Chen Z, Nakamura T. Statistical evidence for the usefulness of Chinese medicine in the treatment of SARS. Phyther Res, 2004,18:592–594.
24. O’Connor SE. Engineering of Secondary Metabolism. Annu Rev Genet. 2015;49:71-94.
25. Thomford NE, Dzobo K, Chopera D, Wonkam A, Skelton M, et al. Pharmacogenomics Implications of Using Herbal Medicinal Plants on African Populations in Health Transition. Pharmaceuticals 2015, 8(3), 637-663.
26. Gulati K, Rai N, Chaudhary S, Ray A. Nutraceuticals in Respiratory Disorders. Nutraceuticals. 2016, Pages 75-86.
27. Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B. 2015 Jul; 5(4): 310–315.
28. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, et al. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003 Jun 14;361(9374):2045-6.
29. Hoever G, Baltina L, Michaelis M, Kondratenko R, Baltina L, et al. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. J Med Chem. 2005 Feb 24;48(4):1256-9.
30. Fiore C, Eisenhut M, Krausse R, Ragazzi E, Pellati D, et al. Antiviral effects of Glycyrrhiza species. Phytother Res. 2008 Feb;22(2):141-8.
31. Ashfaq UA, Masoud MS, Nawaz Z, Riazuddin S. Glycyrrhizin as antiviral agent against Hepatitis C Virus. J Transl Med. 2011; 9: 112.
32. Ito M, Sato A, Hirabayashi K, Tanabe F, Shigeta S, et al. Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV). Antiviral Res. 1988 Dec 11;10(6):289-98.
33. Zhang H, Song Y, Zhang Z. Glycyrrhizin administration ameliorates coxsackievirus B3-induced myocarditis in mice. Am J Med Sci. 2012 Sep;344(3):206-10.
34. Soufy H, Yassein S, Ahmed AR, Khodier MH, Kutkat MA et al. Antiviral and immune stimulant activities of glycyrrhizin against duck hepatitis virus. Afr J Tradit Complement Altern Med. 2012 Apr 2;9(3):389-95.
35. Wang J, Chen X, Wang W, Zhang Y, Yang Z, et al. Glycyrrhizic acid as the antiviral component of Glycyrrhiza uralensis Fisch. against coxsackievirus A16 and enterovirus 71 of hand foot and mouth disease. J Ethnopharmacol. 2013 May 2; 147(1): 114–121.
36. Yu M, Lee J, Lee JM, Kim Y. Identification of myricetin and scutellarein as novel chemical inhibitors of the SARS coronavirus helicase, nsP13. April 2012. Bioorganic & medicinal chemistry letters 22(12):4049-54.
37. Sirion U, Kasemsuk T, Suksen K, Piyachaturawat P. Bioorganic & Medicinal Chemistry Letters 22 (2012) 49–52. January 2016.
38. Achan J, Talisuna AO, Erhart A, Yeka A, Tibenderana JK, et al. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria. Malar J. 2011 May 24;10:144.
39. De Leo M, Braca A, Sanogo R, Cardile V, DeTommasi N, Russo A. Antiproliferative activity of Pteleopsis suberosa leaf extract and its flavonoid components in human prostate carcinoma cells. Planta Med. 2006 Jun; 72(7):604-10.
40. Kong NN, Fang ST, Wang JH, Wang ZH, Xia CH. Two new flavonoid glycosides from the halophyte Limonium franchetii. J Asian Nat Prod Res. 2014; 16(4):370-5.
41. Wang L, Yang R, Yuan B, Liu Y, Liu C. The antiviral and antimicrobial activities of licorice, a widely-used Chinese herb. Acta Pharm Sin B. 2015 Jul; 5(4): 310–315.
42. Ghannad MS, Mohammadi A, Safiallahy S, Faradmal J, Azizi M, et al. The Effect of Aqueous Extract of Glycyrrhiza glabra on Herpes Simplex Virus 1. Jundishapur J Microbiol. 2014 Jul; 7(7): e11616.
43. Michaelis M, Geiler J, Naczk P, Sithisarn P, Leutz A, et al. Glycyrrhizin Exerts Antioxidative Effects in H5N1 Influenza A Virus-Infected Cells and Inhibits Virus Replication and ProInflammatory Gene Expression. PLoS One. 2011; 6(5): e19705.
44. Gautret P, Lagier J, Parola P, Hoang VT, Meddeb L, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. Int J Antimicrob Agents. 2020 Jul;56(1):105949.
45. Große M, Ruetalo N, Businger R, Rheber S, Setz C. Evidence That Quinine Exhibits Antiviral Activity against SARS-CoV-2 Infection In Vitro. life sciences. Virology. 202007.0102.v1.
46. Ryu YB, Jeong HJ, Kim JH, Kim YM, Park J, et al. Biflavonoids from Torreya nucifera displaying SARS-CoV 3CLpro inhibition. Bioorganic & Medicinal Chemistry. Volume 18, Issue 22, 15 November 2010, Pages 7940-7947.
47. Kao RY, Tsui WH, Lee TS, Tanner JA, Watt RM. Identification of novel small-molecule inhibitors of severe acute respiratory syndrome-associated coronavirus by chemical genetics. Chem Biol. 2004 Sep; 11(9):1293-9.
48. Li F, Song X, Su G, Wang Y, Wang Z et al. Amentoflavone Inhibits HSV-1 and ACV-Resistant Strain Infection by Suppressing Viral Early Infection. Viruses. 2019 May; 11(5): 466.
49. Lin C, Tsai F, Tsai C, Lai C, Wan L, Ho T et al. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica root and plant-derived phenolic compounds. Antiviral Res. 2005 Oct;68(1):36- 42.
50. Ho T, Wu S, Chen J, Hsiang C. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antivir Res. 2007;74(2):92–101.
51. Dai J, Wang Q, Su Y. Emodin inhibition of influenza A virus replication and influenza viral pneumonia via the Nrf2, TLR4, p38/JNK and NF-kappaB pathways. Molecules. 2017;22(10).
52. Lin S, Ho C, Chuo W, Li S, Tony T, et al. Effective inhibition of MERS-CoV infection by esveratrol. BMC Infect Dis. 2017 Feb 13;17(1):144.
53. Malaguarnera L. Influence of Resveratrol on the Immune Response. Nutrients. 2019 May; 11(5): 946.
54. Lin S, Ho C, Chuo W, Li S, Wang TT. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect Dis. 2017; 17: 144.
55. Obeid S, Alen J, Nguyen VH, Pham VC, Meuleman P, et al. Artemisinin Analogues as Potent Inhibitors of In Vitro Hepatitis C Virus Replication. PLoS One. 2013; 8(12): e81783.
56. Posner GH, Chang W, Hess L, Woodard L, Sinishtaj S, et al. Malaria-infected mice are cured by oral administration of new artemisinin derivatives. J Med Chem. 2008 Feb 28; 51(4):1035-42.
57. Messori L, Gabbiani C, Casini A, Siragusa M, Vincieri FF, et al. The reaction of artemisinins with hemoglobin: a unified picture. Bioorg Med Chem. 2006 May 1; 14(9):2972-7.
58. Meshnick SR. Artemisinin: mechanisms of action, resistance and toxicity. Int J Parasitol. 2002 Dec 4; 32(13):1655-60.
59. Efferth T, Marschall M, Wang X, Huong SM, Hauber I, et al. Antiviral activity of artesunate towards wild-type, recombinant, and ganciclovir-resistant human cytomegaloviruses. J Mol Med (Berl). 2002 Apr; 80(4):233-42.
60. Want MY, Islammudin M, Chouhan G, Ozbak HA, Hemeg HA, et al. Nanoliposomal artemisinin for the treatment of murine visceral leishmaniasis. Int J Nanomedicine. 2017; 12: 2189–2204.
61. Cao R, Hu H, Li Y, Wang X, Xu M, et al. Anti-SARS-CoV-2 Potential of Artemisinins In Vitro. ACS Infect Dis. 2020 Jul 31: acsinfecdis.0c00522.
62. Gilmore K, Osterrieder, K, Seeberger PH. Extracts of the plant A. annua are active against SARSCoV-2. Cooperation between scientists from the Max Planck Institute, University of Kentucky and Freie Universität Berlin. № 107/2020 from Jun 24, 2020.
63. Prasad A, Muthamilarasan M, Prasad M. Synergistic antiviral effects against SARS-CoV-2 by plant-based molecules. Plant Cell Rep. 2020 Sep;39(9):1109-1114.
64. Sheng-Dian H, Yu Z , Hong-Ping HE , Shi-Fei L, Gui-Hua T, et al. A new Amaryllidaceae alkaloid from the bulbs of Lycoris radiata. Chinese Journal of Natural Medicines 2013, 11(4): 0406 0410.
65. Li S, Chen C, Zhang H, Guo H, Wang H, et al. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res. 2005 Jul; 67(1): 18–23.
66. Fuzimotoa AD, and Isidoro C. The antiviral and coronavirus-host protein pathways inhibiting properties of herbs and natural compounds – Additional weapons in the fight against the COVID19 pandemic? J Tradit Complement Med. 2020 Jul; 10(4): 405–419.
67. Chen F., Chan K., Jiang Y. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. 2004;31(1):69–75.
68. Jia W, Gao W. Is traditional Chinese medicine useful in the treatment of SARS? Phytother Res. 2003 Aug;17(7):840-1.
69. Ravishankar B., Shukla V. Indian systems of medicine: a brief profile. Afr. J. Trad. Complement. Altern. Med. 2007;4:319–337.
70. Pundarikakshudu K., Kanaki N.S. Analysis and regulation of traditional Indian medicines (TIM) J. AOAC Int. 2019;102:977–978.
71. Yuan H., Ma Q., Ye L., Piao G. The traditional medicine and modern medicine from natural products. Molecules. 2016;21:559.
72. Parasuraman S, Thing GS, Dhanaraj SA. Polyherbal formulation: concept of ayurveda. Pharmacogn. Rev. 2014;8:73.