|Year : 2020 | Volume
| Issue : 2 | Page : 132-138
Antiviral properties of traditional chinese medicine against coronavirus: Research clues for coronavirus disease-2019
Xu-Jie Wang1, Jia-Xi Li2, Miao-Ran Wang3, Zhong-Yang Zhou4, Bao-Chen Zhu5, Xue-Xue Zhang1, Rui Zhang3, Wei Tang3, Yu-Fei Wu3, Wan-Tong Zhang2, Qiu-Yan Li2
1 Xiyuan Hospital, China Academy of Chinese Medical Sciences; Graduate School, China Academy of Chinese Medical Sciences, Beijing, China
2 Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
3 Xiyuan Hospital, China Academy of Chinese Medical Sciences; Beijing University of Chinese Medicine, Beijing, China
4 Xiyuan Hospital, China Academy of Chinese Medical Sciences; Community Health Service Center of Beizhuang Town, Beijing, China
5 Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
|Date of Submission||21-Mar-2020|
|Date of Acceptance||25-Mar-2020|
|Date of Web Publication||30-May-2020|
Prof. Qiu-Yan Li
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091
Dr. Wan-Tong Zhang
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091
Source of Support: None, Conflict of Interest: None
The objective of this study was to provide research clues for the prevention and treatment of coronavirus disease-2019 (COVID-19) and coronavirus (CoV) infection using Traditional Chinese Medicine (TCM). A review on research and clinical trials that using TCM extracts and active ingredients against CoV was performed, and a table of TCM agents and their effects on CoV were summarized. Relevant analysis was performed and visual expression of the data included summarizing the types of TCM and treatment methods for COVID-19. TCM fighting against CoV is mainly used in the lung and heart channels, and its medicinal properties are mainly cold and mild, while its taste is mainly bitter and sweet. The majority of research focused on treatments that clear away heat and toxic materials and those that strengthen body resistance and tonify deficiencies. TCM has unique advantages to fight against CoV. The development of new anti-CoV therapy using TCM is of great significance for the prevention and treatment of COVID-19 pneumonia and various viral infectious diseases.
Keywords: 2019-novel coronavirus, coronavirus, coronavirus disease-19, novel coronavirus pneumonia, severe acute respiratory syndrome-coronavirus-2, Traditional Chinese Medicine
|How to cite this article:|
Wang XJ, Li JX, Wang MR, Zhou ZY, Zhu BC, Zhang XX, Zhang R, Tang W, Wu YF, Zhang WT, Li QY. Antiviral properties of traditional chinese medicine against coronavirus: Research clues for coronavirus disease-2019. World J Tradit Chin Med 2020;6:132-8
|How to cite this URL:|
Wang XJ, Li JX, Wang MR, Zhou ZY, Zhu BC, Zhang XX, Zhang R, Tang W, Wu YF, Zhang WT, Li QY. Antiviral properties of traditional chinese medicine against coronavirus: Research clues for coronavirus disease-2019. World J Tradit Chin Med [serial online] 2020 [cited 2020 Jul 5];6:132-8. Available from: http://www.wjtcm.net/text.asp?2020/6/2/132/285410
| Introduction|| |
Coronavirus (CoV) is an enveloped positive-sense single-stranded RNA virus of the family Coronaviridae and is of the order Nidovirales. It is named because of the pleomorphic Corolla process observed on the surface of this kind of virus. CoV is a pathogen that causes diseases in a variety of wild animals, livestock, and human beings. CoV is divided into four genera (α, β, γ, and δ) according to gene sequence, serotype relationships, and natural hosts by the International Committee on Taxonomy of Viruses. Severe acute respiratory syndrome (SARS)-CoV, SARS-CoV-2 (2019-novel CoV [nCoV]), and Middle East respiratory syndrome (MERS)-CoV belong to the β genus.
Notably, there are a large number of variable translations in the genome of beta-CoV (β-CoV), which is characterized by high diversity and rapid variation. Nevertheless, studies have shown that 2019-nCoV has more than 85% homology with bat-SL-CoVZC45 and bat-SL-CoVZXC21, and about 79% homology with SARS-CoV, and both have similar receptor-binding domains (ACE2 receptors). In addition, there is a highly conserved sequence (Nankai CDS) in the genome of β-CoV, which rarely mutates.,
Therefore, research on the SARS-CoV, MERS-CoV, and other coronaviruses can be beneficial for the development of clinical treatments for coronavirus disease-2019 (COVID-19) patients and may inform us of the prevention and treatment methods to inhibit this kind of novel CoV.
| Summary of Anticoronavirus Traditional Chinese Medicine and Related Preparations|| |
Since the outbreak of SARS, research and treatment for various coronaviruses have rapidly emerged, among which the research on antiviral components of natural drugs is prevalent. Practice has proved that treatment with Traditional Chinese Medicine (TCM) can interfere with respiratory diseases caused by CoV in varying degrees. Moreover, a variety of effective components contained in TCM can inhibit the replication of CoV. The author summarizes and analyzes the research in recent years on the use of TCM to treat CoV, which can provide a basis for the discovery of novel anti-CoV drugs.
Types of Chinese medicine effective against severe acute respiratory syndrome coronavirus
SARS-associated CoV is highly pathogenic and belongs to the subgroup B of β-CoV. It has the epidemiological characteristics of being highly infectious, rapidly progressing, and causing severe disease in human beings. From 2002 to 2003, SARS-CoV spreads to more than 30 countries and regions around the world with more than 8000 people being infected and a fatality rate of approximately 10%. After the outbreak of SARS, governments and organizations in various countries began to attach great importance to research on this kind of CoV. The whole genome of SARS-CoV was rapidly deciphered, and research and development of antiviral drugs and vaccines were promoted. However, due to many unfavorable factors such as virus mutation, this problem could not be solved completely. Because the practice of syndrome differentiation is effective in the treatment of SARS, the health department of China has always incorporated these methods into treatment plans. A large number of studies have proved that a variety of TCM treatments have an inhibitory effect on SARS-CoV, as detailed in [Table 1].
|Table 1: Active ingredients and effects of Traditional Chinese Medicine on severe acute respiratory syndrome-related coronavirus|
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Types of Chinese medicine effective against beta-coronavirus
The genomic structure of β-CoV is relatively complex and includes four subgroups (A, B, C, and D). Subgroup A includes two kinds of human CoV (HCoV-OC43 and HCoV-HKU1), mouse hepatitis virus, bovine CoV, etc.; Subgroup B includes SARS-CoV and SARS-Rh-BatCoV-HKU3; Subgroup C includes MERS-CoV and two bat coronaviruses; Subgroup D contains Ro-BatCoV-HKU9. At present, five of the seven known human coronaviruses belong to the β-genus, of which three are highly pathogenic coronaviruses, namely, SARS-CoV, MERS-CoV, and SARS-CoV-2. These viruses have a high fatality rate when they infect humans, with MERS-CoV reaching rates as high as 36%.
Because of the high homology among the viruses of the same genus, there is no specific treatment for this kind of infection and an effective preventive vaccine has not yet been developed. Thus, understanding this genus is key to solving many problems associated with coronaviruses. Countries around the world have attached great importance to this by performing extensive research and exploration including TCM treatments, as detailed in [Table 2].
|Table 2: Active ingredients and effects of Traditional Chinese Medicine targeting β coronavirus|
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Types of Chinese medicine effective against alpha- coronavirus
Alpha CoV (α-CoV) can be divided into two subgroups: α 1 and α 2. α 1 subgroup includes feline infectious peritonitis virus, canine CoV, etc., and α 2 Subgroup includes two kinds of hCoV (HCoV-NL63 and HCoV-229E), porcine epidemic diarrhea virus (PEDV), etc.
HCoV-229E is the earliest isolated hCoV, and it is a common CoV strain with global distribution currently. Like HCoV-NL63, the respiratory symptoms caused by the two viruses are mild, the course of disease is short, and clinical treatment can effectively control the development of the disease., PEDV is a type of enterovirus and the mortality rate of piglets is very high after infection. Spread of this virus has occurred in many countries and caused serious economic losses. The study of α-CoV is also very necessary, and the ingredients contained in TCM are capable of inhibiting it, as detailed in [Table 3].
|Table 3: Active ingredients and effects of anti-α coronavirus Traditional Chinese Medicine|
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Types of Chinese medicine effective against gamma- coronavirus
Gamma-CoV mainly infects birds and some marine mammals and includes infectious bronchitis virus (IBV) and beluga whale coronavirus (SW1). IBV is a highly infectious pathogen for poultry. Poultry infected with IBV will develop serious respiratory symptoms resulting in death that has led to significant economic losses to the poultry industry. The nucleotide sequence homology of IBV and SARS-CoV is close, and there is a certain genetic relationship, which has led some scholars to use IBV as a model for CoV in studies measuring the inhibition capacity of TCM, as shown in [Table 4].
|Table 4: Active ingredients and effects of Traditional Chinese Medicine targeting γ coronavirus|
Click here to view
| Data Analysis and Visual Expression|| |
Treatments were analyzed based on syndrome differentiation of disease caused by CoV and details from the theory of TCM. In order to make the data in the [Table 1], [Table 2], [Table 3], [Table 4] more intuitive, we synthesized the known data in the above literature using the ancient and modern medical record cloud platform Personal Edition version 2.2.1 as was well as the Cytoscape 3.7.2 (U.S. National Institute of General Medical Sciences (NIGMS) )drawing software to carry out the relevant statistical analysis and visual expression of the data.
Properties of Traditional Chinese Medicine against coronavirus
The results of Chinese medicinal nature and flavor show that the medicinal properties are mainly cold and plain, and the flavor of these medicines is mainly bitter and sweet. The results of channel tropism showed that this kind of TCM is mostly in the meridians of the lung and heart [Figure 1], [Figure 2], [Figure 3].
Efficacy of Traditional Chinese Medicine against coronavirus
From the analysis using the ancient and modern medical record cloud platform software, we know that most of the above drugs belong to two categories: eliminating pathogenic factors and strengthening vital qi. The most common antipathogenic drugs are involved in “clearing heat and removing toxicity”,”cooling blood and clearing heat” and “removing phlegm and relieving cough. In contrast, the drugs for strengthening vital qi are “nourishing liver and kidney,” “relieving pain” and “tonifying spleen qi.”
Active components of Traditional Chinese Medicine against coronavirus
Next, we collected the information from different TCM treatments for CoV along with the effective ingredients of these therapies. Using the drawing software Cytoscape 3.7.2 (https://cytoscape.org/) to integrate the effective components of TCM with the viruses that they inhibit, we created a Network Diagram of Efficacy and Drug Composition [Figure 4].
| Discussion|| |
The antiviral mechanisms of TCM include viral replication inhibition in host cells, inhibition of virus adsorption or invasion into host cells, and regulation of the human immune system. The active components of each TCM interfere with unique steps in the process of viral invasion into host cells. At present, the research on the antiviral activity of TCM extracts and their active components is mainly focused on the mechanism of action at the cellular and molecular level in vitro, which can be used for reference in clinic; however, it should be correctly distinguished from the actual use of drugs andin vivo treatments or clinical trials.
Strengthening vital qi to eliminate pathogenic factors
Combined with the above analysis, most of the TCMs with antiviral properties are mainly “clearing heat and removing toxicity” with some medicines acting by “Strengthening vital qi and consolidating body resistance.” According to the latest research, in the diagnosis and treatment programs of TCM for the prevention and treatment of pneumonia caused by SARS-CoV-2 infection, COVID-19 pneumonia has mainly been identified as an epidemic disease caused by the evil of “dampness-heat toxicity and blood stasis.” Importantly, the recommended prescriptions of TCM and proprietary Chinese medicine for COVID-19 pneumonia are compound prescriptions for clearing heat and removing toxicity. However, at the same time, the disease does great damage to the vital qi of patients, and “deficiency” is also one of the main characteristics of this epidemic disease. Through the accurate prescription of treatment based on syndrome differentiation, we can improve the human body's ability to resist the invasion of external illness and maintain a healthy qi in the inner body. We hope to prevent the epidemic as well as avoid the creation of pathogenic qi. Thus, it can be seen that “strengthening vital qi to eliminate pathogenic factor” is the basic antiviral treatment mechanism in TCM.
Comprehensive analysis of data gained by two effects
”Two effects” refers to both effective antivirals and effective clinical syndrome differentiation. The external symptoms of different diseases vary, and the manifestation of the same disease may differ from one individual to the next. It is necessary to use the overall concept of time, place, and personal conditions. For the treatment of all infectious diseases in TCM, we must adhere to treating through the principle of comprehensive analysis based on data from the four diagnostic methods and treatment based on syndrome differentiation. On this basis, it may be more beneficial to the overall clinical effect to add TCM, which has been proven to have antiviral capacity, to modern pharmacology.
| Conclusion|| |
The antiviral mechanism of TCM is the result of many factors. As a natural form of medicine, most TCM treatments have the advantage of broad-spectrum antiviral coverage, good curative effect, and low side effect profiles. The field of TCM antiviral treatments has broad prospects. The research and development of these treatments is of great significance for the prevention and treatment of COVID-19 pneumonia other sequelae caused by SARS-CoV-2.
Financial support and sponsorship
We thank Professor Weng Wei-liang, a famous Chinese medicine practitioner, for his academic guidance on this article. This study was supported by the third National Medicine Master's Inheritance Studio Construction Project of the State Administration of TCM (Weng Wei-liang Academic Succession Studio) and Beijing Traditional Chinese Medicine's Succession “3 + 3” Project (Weng Wei-liang Academic Succession Workstation).
Conflicts of interest
There are no conflicts of interest.
| References|| |
Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, et al
. Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020;395:565-74.
Yang H, Bartlam M, Rao Z. Drug design targeting the main protease, the Achilles' heel of coronaviruses. Curr Pharm Des 2006;12:4573-90.
Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003;361:2045-6.
Hoever G, Baltina L, Michaelis M, Kondratenko R, Baltina L, Tolstikov GA, et al
. Antiviral activity of glycyrrhizic acid derivatives against SARS-coronavirus. J Med Chem 2005;48:1256-9.
Lu H, Huo N, Wang G, Li H, Nie L, Xu X. Clinical Observation of Therapeutic Effect of Compound Glycyrrhizin on SARS[J]. China Pharmacy,2003;10:34-6.
Wen CC, Shyur LF, Jan JT, Liang PH, Kuo CJ, Arulselvan P, et al
. Traditional Chinese Medicine herbal extracts of Cibotium barometz, Gentiana scabra, Dioscorea batatas, Cassia tora
, and Taxillus chinensis
inhibit SARS-CoV replication. J Tradit Complement Med 2011;1:41-50.
] [Full text]
Li SY, Chen C, Zhang HQ, Guo HY, Wang H, Wang L, et al
. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res 2005;67:18-23.
Park JY, Yuk HJ, Ryu HW, Lim SH, Kim KS, Park KH, et al
. Evaluation of polyphenols from Broussonetia papyrifera
as coronavirus protease inhibitors. J Enzyme Inhib Med Chem 2017;32:504-15.
Song YH, Kim DW, Curtis-Long MJ, Yuk HJ, Wang Y, Zhuang N, et al
. Papain-like protease (PLpro) inhibitory effects of cinnamic amides from Tribulus terrestris
fruits. Biol Pharm Bull 2014;37:1021-8.
Yang QY, Tian XY, Fang WS. Bioactive coumarins from Boenninghausenia sessilicarpa
. J Asian Nat Prod Res 2007;9:59-65.
Chen CJ, Michaelis M, Hsu HK, Tsai CC, Yang KD, Wu YC, et al
. Toona sinensis
roem tender leaf extract inhibits SARS coronavirus replication. J Ethnopharmacol 2008;120:108-11.
Lin CW, Tsai FJ, Tsai CH, Lai CC, Wan L, Ho TY, et al
. Anti-SARS coronavirus 3C-like protease effects of Isatis indigotica
root and plant-derived phenolic compounds. Antiviral Res 2005;68:36-42.
Yi L, Li Z, Yuan K, Qu X, Chen J, Wang G, et al
. Small molecules blocking the entry of severe acute respiratory syndrome coronavirus into host cells. J Virol 2004;78:11334-9.
Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW, et al
susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 2004;31:69-75.
Lau KM, Lee KM, Koon CM, Cheung CS, Lau CP, Ho HM, et al
. Immunomodulatory and anti-SARS activities of Houttuynia cordata
. J Ethnopharmacol 2008;118:79-85.
Ho TY, Wu SL, Chen JC, Li CC, Hsiang CY. Emodin blocks the SARS coronavirus spike protein and angiotensin-converting enzyme 2 interaction. Antiviral Res 2007;74:92-101.
Gong S, Su X, Yu H, Li J, Tan Y, Xu Q, et al
. A study on anti-SARS-CoV 3CL protein of flavonoids from litchi chinensis sonn core[J]. Chinese Pharmacol ogical Bulletin,2008,05:699-700.
Wang B. Screening SARS Coronavirus Main Protease Inhibitors from Natural Products [D]. Nankai University,2012;65-77. DOI:10.7666/d.Y2525252.
Li G, Pan L. Research development of genome structure and related protein of coronavirus. J Northeast Agric Univ 2013;44:149-54.
Chan JF, Lau SK, To KK, Cheng VC, Woo PC, Yuen KY. Middle East respiratory syndrome coronavirus: Another zoonotic betacoronavirus causing SARS-like disease. Clin Microbiol Rev 2015;28:465-522.
Lin SC, Ho CT, Chuo WH, Li S, Wang TT, Lin CC. Effective inhibition of MERS-CoV infection by resveratrol. BMC Infect Dis 2017;17:144.
Yi W. An Experiental Study on the Effect of Shuang-huang-lian, Herba Houttuyniae and Allitridin against Murine Hepatitis Virus type 3 in vitro
and in vivo
[D].HUAZHONG UNIVERSITY OF SCIENCE AND TECHNOLOGY,2006;47-60. DOI:10.7666/d.y961710.
Dong X. Research progress of human coronaviruses HcoV 229E. Occupation and Health 2014;30:3625-7, 31.
Li N, Jing S, Zeng W. Develop outline of human coronavirus HcoV-NL63. J Yunnan Univ (Nat Sci Ed) 2009;31 (Suppl 1):499-501, 8.
Zhang B, Chen J, Xing Y, Feng L, Chen Z, et al.
Porcine Epidemic Diarrhea Virus (PEDV) and Host Antiviral Innate Immunity[J]. Chinese Journal of Biochemistry and Molecular Biology,2011;27:516-23.
Weng JR, Lin CS, Lai HC, Lin YP, Wang CY, Tsai YC, et al
. Antiviral activity of Sambucus Formosana Nakai
ethanol extract and related phenolic acid constituents against human coronavirus NL63, Virus Res 2019;273:197767.
Chang FR, Yen CT, Ei-Shazly M, Lin WH, Yen MH, Lin KH, et al
. Anti-human coronavirus (anti-HCoV) triterpenoids from the leaves of Euphorbia neriifolia
. Nat Prod Commun 2012;7:1415-7.
Song JH, Shim JK, Choi HJ. Quercetin 7-rhamnoside reduces porcine epidemic diarrhea virus replication via independent pathway of viral induced reactive oxygen species. Virol J 2011;8:460.
Kwon HJ, Ryu YB, Kim YM, Song N, Kim CY, Rho MC, et al
antiviral activity of phlorotannins isolated from ecklonia cava against porcine epidemic diarrhea coronavirus infection and hemagglutination. Bioorganic Med Chem 2013;21:4706-13.
Kim JW, Ha TK, Cho H, Kim E, Shim SH, Yang JL, et al
. Antiviral escin derivatives from the seeds of Aesculus turbinata
blume (Japanese horse chestnut). Bioorg Med Chem Lett 2017;27:3019-25.
Huang M, Zhang Y, Xue C, Cao Y. To meet the growing challenge: research of avian infectious bronchitis in China [J]. Microbiology China,2019;7:1837-49.
Lin Q. The Basic Research of Indigotica Fort to Restrain Avian Infectious Bronchitis Virus(IBV)[D]. Guangzhou University of Chinese Medicine 2014;43-57.
Qiu Y, Hu YL, Cui BA, Zhang HY, Kong XF, Wang DY, et al
. Immunopotentiating effects of four Chinese herbal polysaccharides administered at vaccination in chickens. Poult Sci 2007;86:2530-5.
Yin J, Li G, Li J, Yang Q, Ren X.In vitro
effects of Houttuynia cordata
on infectious bronchitis virus. Avian Pathol 2011;40:491-8.
Sun L. Experimental Studies of the Effects of a Chinese Herbal Medical Compound Formula-Kangliyin on an Animal Model of Respiratory Coronavirus Infection[D]. Guangzhou University of Chinese Medicine,2006;46-65.
Li H, Wu J, Zhang Z, Ma Y, Liao F, Zhang Y, et al
. Forsythoside a inhibits the avian infectious bronchitis virus in cell culture. Phytother Res 2011;25:338-42.
Sun C, Chen J. Review of antiviral mechanism of Traditional Chinese Medicine. Light Ind Sci Technol 2016:8:27-8.
Gao R, Yan B. Research overview on antiviral mechanism of Chinese medicine. J Shandong Univ Tradit Chinese Med 2015:5:480-3.
Zheng W, Zhang J, Yang F, Wang Y, Liu Q, Zhang B. Comprehensive Analysis of Diagnosisand Treatment Schemes for Prevention and Treatment of Novel Coronavirus Pneumonia by Traditional Chinese Medicine[J]. Journal of Traditional Chinese Medicine,2020;61:277-80.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]