Skip to main content

Effect of herbal compounds on coronavirus; a systematic review and meta-analysis



The new coronavirus (COVID-19) has been transmitted exponentially. Numerous studies have been performed in recent years that have shown the inhibitory effect of plant extracts or plant-derived compounds on the coronavirus family. In this study, we want to use systematic review and meta-analysis to answer the question, which herbal compound has been more effective?

Main body

The present study is based on the guidelines for conducting meta-analyzes. An extensive search was conducted in the electronic database, and based on the inclusion and exclusion criteria, articles were selected and data screening was done. Quality control of articles was performed. Data analysis was carried out in STATA software.


Due to the variety of study methods, definitive conclusions are not possible. However, in this study, we attempted to gather all the available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against this virus and other coronaviruses. Trypthantrin, Sambucus extract, S. cusia extract, Boceprevir and Indigole B, dioica agglutinin urtica had a good effect on reducing the virus titer. Also among the compounds that had the greatest effect on virus inhibition, Saikosaponins B2, SaikosaponinsD, SaikosaponinsA and Phillyrin, had an acceptable selectivity index greater than 10. Andrographolide showed the highest selectivity index on SARS-COV-2. Our study confirmed insufficient data to support alkaloid compounds against SARS-COV-2, and the small number of studies that used alkaloid compounds was a limitation. It is recommended to investigate the effect of more alkaloid compounds against Corona virus.


The outbreak of the new coronavirus (COVID-19) originated in Wuhan, China in December 2019 and has affected many countries around the world. As of March 26, the World Health Organization (WHO) has announced in detail that the disease has spread to 197 countries. Most people infected with the COVID-19 virus experience mild to moderate respiratory illness and recover without special treatment [15, 58]. The elderly and those with underlying medical problems such as cardiovascular disease, diabetes, chronic respiratory disease, and cancer develop serious illness [5, 17].

For providing the best immunization to the community against this virus, alongside developed vaccines, different drugs are still needed for coronavirus inhibition [49]. Remdesivir (Veklury) is currently the only FDA approved drug to treat coronavirus disease. This confirmation was based on findings that hospitalized patients who received Remdesivir recovered faster. Many clinical trials are currently underway to evaluate other potential therapies, such as monoclonal antibodies to COVID-19. Researchers are also testing older drugs (commonly used to treat other diseases) to see if they work for COVID-19.

Plants have beneficial biomedical effects due to their natural properties [33, 42]. Plants are inexpensive and available sources of medicinal compounds that by changing the growth conditions and the effect of various stimulants, the production of medicinal molecules and their effect can be increased several times [3, 12, 41, 43]. The antiviral effects of many plants have been proven. Of course, plants that have previously had an inhibitory effect on the coronavirus family or inhibited the ACE2 enzyme may help inhibit new coronavirus or symptomatic therapy [39].

Traditional herbal medicines have been used since the early days of COVID-19 in China. These traditional drugs have been shown to improve 90% of the 214 patients [14]. Some traditional herbal therapies stopped SARS-COV-2 infection in healthy people and improved the health status of patients with mild or severe symptoms [14, 54]. Traditional Chinese medicine known as Shu Feng Jie Du and Lianhuaqingwen, which have been effective against previous influenza A (H1N1) or SARS-CoV-1 [30], have been recommended. The use of traditional medicines in COVID-19 treatment and prevention guidelines was prepared by a team from Wuhan University's Zhongnan Hospital. Several methods using herbs have been suggested to prevent COVID-19. In addition, for the treatment of the disease, experts recommended the use of different herbal mixtures according to the stage of the disease [19]. Evidence suggests that herbal remedies may be effective in decreasing and managing of COVID-19 risk [13]. Despite many primary study researches, there is no a systematic review article that compare the effects of all studied compounds on the SARS-COV-2 by more details and it can be useful for researchers in this field.

In this study, we conducted a systematic review and meta-analysis on herbal compounds against coronavirus family, which may have the potential in treating COVID19 infection. The purpose of this study is to better understand current compounds in research into the development of new antiviral agents against SARS-COV-2 from plant sources. The findings of this study can help to provide up-to-date knowledge about the antiviral potential against SARS-COV-2 in medicinal plants and to utilize existing knowledge gaps to improve future research by identifying areas for greater focus.


The present study is designed based on the PRISMA guidelines for systematic review. The present study investigated the inhibitory effect of plant compounds on the coronaviruses family.

Search strategy

An extensive search of the Medline electronic database, ISI Web of Science, EMBASE, and Scopus was conducted through April 2021. The search strategy was based on the Table 1. Keywords have been selected as widely as possible so that a study is not omitted. To find additional articles or unpublished data, hand-search was performed in the list of relevant articles and related journals.

Table 1 Keywords for search of the databases

Inclusion and exclusion criteria

Controlled in-vitro and in-vivo studies were selected to investigate the inhibitory effect of plant compounds against each of the coronaviruses. Controlled studies are studies that, in addition to a group treated with a plant composition, also have a control group without treatment. No time or language restrictions were imposed. Because most viral studies are performed in an in-vitro model, the target population for this study is SARS-COV-2 virus-infected cells.In the present study, short articles and letters to the editor were not examined. Review articles were not included in the study.


In the present study, the Selectivity Index (SI) (the CC50/EC50 ratio) was extracted from articles. CC50 is the concentration of compound required to reduce host cell viability by 50% and EC50 is the concentration of compound required to reduce virus function by 50%. In addition, studies that have examined each of the factors of inhibition of virus and virus titer are included in the meta-analysis.

The extracted articles were evaluated independently by two researchers and the data were recorded in the data extraction form. In case of disagreement between two researchers, the third person studied the findings and resolved the existing disagreement by discussing and exchanging views with the other two researchers. Data collection was done without prejudice and restrictions on the author, journal, organization or organ. The results of a systematic search in this study were recorded in a checklist designed based on PRISMA statement guidelines. The extracted data included general information of the article (author name, year of publication), information related to the design of the study, characteristics of the studied host such as cell type, as well as characteristics of the studied plant such as plant name and strain. When the consequences and values ​​to be evaluated are reported in several stages, the last evaluation time was entered into the research. If the results were presented in the form of graphs, the data extraction method was used.

Quality control

The evaluation of the quality of the studies included in this study has been done according to the methods described in published articles [18, 28]. Eight groups of criteria include 20 items were examined (exclusions, randomization, blinding, sample size, figures and statistical representation of data, definition of statistical methods and measures, implementation of statistical methods and measures, reagents and cells). These criteria were extracted from the articles by the twenty separate cases mentioned below:

(1) Samples that were excluded from the analysis.

(2) Which method of randomization was used to determine how samples were allocated to experimental groups?

(3) Whether the investigator was blinded to the group allocation during the experiment and/or when assessing the outcome,

(4) How the sample size was chosen to ensure adequate power to detect a pre-specified effect size.

(5) Exact sample size (n) for each experimental group/condition was given as a number, not a range.

(6) Whether the samples represented technical or biological replicates.

(7) A statement of how many times the experiment was replicated.

(8) Results were defined as a median or average.

(9) Error bars were defined as SD., SEM. or CI.

(10) Common statistical tests (such as t-test, simple χ2 tests, Wilcoxon and Mann–Whitney tests, or any form of ANOVA testing). If not a common test, is the test is described in the methods section.

(11) If the statistical test used was a t or z test, was it reported as one sided or two sided.

(12) Adjustments for multiple comparisons were applied where appropriate.

(13) The statistical test results (e.g., P values, F statistic etc.) were presented.

(14) The authors show that their data met the assumptions of the tests.

(15) An estimate of variation is reported for each group of data.

(16) The variance between the groups that were statistically compared was comparable (difference less than two-fold).

(17) Every antibody used in the manuscript been characterized by either citation, catalog number, clone number or validation profile,

(18) The source of all cell lines was provided.

(19) The authors reported whether the cell lines used have been recently authenticated.

(20) The authors reported whether the cell lines have recently been tested for contamination (within 6 months of use).


All analyzes were performed using Stata 14. Data were obtained from the mean of different ratios between experimental and control groups. The random effect model was used. Subgroup analysis was performed for the chemical structure of the plant composition used, viral subtype and cell line type studied. P values were reported by testing the statistical hypothesis at the level of 0.05 bilaterally.


Applying exclusion criteria

To reach the studies that met our inclusion criteria (see Fig. 1), we searched the articles and identified 3,589 studies that appeared to be relevant. 1268 studies were duplicates and were omitted. Of the remaining 2328 studies, 47 articles remained after reviewing titles and abstracts. After reviewing the texts of the articles, 15 articles were deleted and 32 articles remained in the study.

Fig. 1
figure 1

PRISMA flow chart for a systematic review with database search details, number of abstracts and retrieved full text displayed

Characteristics of included studies

Table 2 shows the characteristics of the articles included in this study. 15 articles were on SARS-COV, 9 articles were on SARS-COV-2, 6 articles were on HCOV, 3 articles were on IBV, 2 articles were on PEDV and 2 articles were on MERS-COV-2. SI were extracted from 23 studies and EC50 obtained from 16 articles. In 10 articles virus inhibition and in 8 articles virus titer measurements were reported. Other characteristics of the articles such as host cell type, strain and plant genus, drug composition are listed in Table 2.

Table 2 Information about the articles included in this study NR: Not reported, SI: selectivity index, MRC5: human embryonic lung fibroblast

In herbal medicine research, it is common to observe multiple medicinal properties of a plant. It is now well understood that a plant may contain a wide range of chemicals, and have different effects on the virus and the host cell [27]. In this study, SI was one of the indicators extracted from the articles. Awouafack et al. Recommended a SI ≤ 10 acceptance criterion for selecting an active sample [4]. In this study in addition to inhibiting the virus, and reducing the virus titer, the amount of SI was extracted from articles (Table 2).

As shown in Table 2, among all plant compounds, Silvesterol has an SI > 7690 on MERS-COV-2 virus in the host of infected human embryonic lung fibroblast (MRC-5) cell, which has the highest SI. In rank 2, the SI of Saikosaponins B2 was 221 on the HCOV strain.

Of the plant compounds against the SARS-COV strain, Andrographolide had the highest SI. The same compound had the highest SI on SARS-COV-2 (Fig. 2). Then in order honokiol, 7a-hydroxydeoxycryptojaponol, Lycoris radiata, Extract/Amaryllidaceae and Lectin (Man-specific agglutinins) (APA) had the highest SI on SARS-COV strain.

Fig. 2
figure 2

SI value for different compounds on different strains of Coronavirus family. 1. Extract/Yin-Chiau-San, 2. Extract/ Pu-Zhi-Siau-Du-Yien, 3. Extract/ Ger-Gern-Hwang-Lein, 4. Extract/ Sang-Zhiu-Yien, 5. Extract/ Huang-Lein-Zhei-Du-Tang, 6. Extract/ Toona sinensis leaves, 7. Extract/ Toona sinensis leaves, 8. Extract /Amaryllidaceae, 9. Artemisia annua, 10. Pyrrosia lingua, 11. Lindera aggregate, 12. Lycoris radiata, 13. Artemisia annua, 14. Pyrrosia lingua, 15. Lindera aggregate, 16. Lectin (Man-specific agglutinins)(APA), 17. Mannose-specific agglutinins( HHA), 18. Mannose-specific agglutinins( GNA), 19. Mannose-specific agglutinins( NPA), 20. Mannose-specific agglutinins( LRA), 21. Mannose-specific agglutinins(AUA), 22. Mannose-specific agglutinins( CA), 23. Mannose-specific agglutinins( LOA), 24. Mannose-specific agglutinins( EHA), 25. Mannose-specific agglutinins (TLMI), 26. Mannose-specific agglutinins( Morniga M II), 27. GlcNAc-specific agglutinins Nictaba, 28. (GlcNAc)n-specific agglutinins UDA, 29. Gal-specific agglutinins Morniga G II, 30. Man/Glc-specific agglutinins Cladistris, 31. Gal/GalNAc specific agglutinins –PMRIP, 32. GalNAc (> Gal) specific agglutinins/ ML III, 33. GalNAc α (1,3)Gal > GalNAc > Gal-specific agglutinins/IRA, 34. GalNAc α (1,3)Gal > GalNAc > Gal-specific agglutinins/IRA, 35. GalNAc α (1,3)Gal > GalNAc > Gal-specific agglutinins/IRA, 36. Man/GalNAc-specific agglutinins/ TL C II, 37.Lectin (N-acetylglucosamine), 38. Lectin (N-acetylglucosamine), 39.Lectin (N-acetylglucosamine), 40. Lectin (N-acetylglucosamine), 41. Lectin (N-acetylglucosamine), 42. Ferruginol, 43.dehydroabieta-7-one cryptojaponol, 44. 8a-hydroxyabieta-9(11),13-dien-12-one, 45. 7a-hydroxydeoxycryptojaponol, 46. 6,7-dehydroroyleanone, 47.3a,12-diacetoxyabieta-6,8,11,13-tetraene, 48. pinusolidic acid, 49.forskolin, 50.α –cadinol, 51.betulinicacid, 52. betulonic acid, 53. Savinin, 54.honokiol, 55.magnolol, 56.supernatant of Cibotium barometz, 57.dried rhizome of Gentiana scabra, 58 tuber of Dioscorea batatas, 59. dried seed of Cassia tora, 60. dried stem, with leaf of Taxillus chinensis, 61. Forsythiae Fructus, 62. Scutellariae Radix, 63. Astragali Radix, 64. Bupleuri Radix, 65. Glycyrrhizae Radix, 66. Cinnamomi Cortex (CCE), 67. Ethanol extract of CC (Fr.1), 68. Butanol fraction of CC (Fr.2), 69. Aqueous fraction of CC (Fr.3), 70. Ethylacetate fraction of CC (Fr.4), 71. Caryophylli Flos (CFE), 72. Ethanol extract of CF (Fr.1), 73. Butanol fraction of CF (Fr.2), 74. Aqueous fraction of CF (Fr.3), 75. Ethylacetate fraction of CF (Fr.4), 76. Arteether, 77. artemether, 78. artemisicacid, 79. artemisinin, 80. artemisone, 81. dihydroartemisinin, 82. artesunate, 83. arteannuin, 84. lumefantrine, 85. andrographolide, 86. andrographolide, 87. andrographolide, 88. andrographolide, 89. andrographolide, 90. andrographolide, 91. Phillyrin (KD-1), 92. Liu Shen capsule, 93. Griffithsin, 94. Glycyrrhizin, 95. L. nobilis, 96. T. orientalis, 97. J. oxycredrus ssp, 98. Pyramidalis, 99. P. palaestina, 100. P. palaestina, 101. S. officinalis, 101. Glycyrrhizin

Among the compounds acting on the PEDV strain, Oleanane triterpenes6 showed the highest SI = 44.54, followed by Oleanane triterpenes9. Among the compounds acting on IBV, the ethanolic extract of Lamiaceae showed the highest SI (Fig. 2).

The EC50 (Table 2), was reported in articles with two units of µg/ml and µM/L, and therefore we divide the articles into two groups according to the reported unit in our studies. In studies that investigated the EC50 of plant composition on SARS-COV and reported the result as µg/ml Lectin (Man-specific agglutinins) (EC50 = 0.45 ± 0.08 (µg/ml), Griffithsin (EC50 = 0.61 µg/ml), Mannose-specific agglutinins (EC50 = 1.6 ± 0.5 (µg/ml) and GlcNAc-specificictc Nictaba agglutinins (EC50 = 1.7 ± 0.3 (µg/ml), (GlcNAc) n-specific agglutinins UDA (EC50 = 1.3 ± 0.1 (µg/ml), extract of Amaryllidaceae (EC50 = 2.4 (± 0.2) (µg/ml) and extract of Lycoris radiate (EC50 = 2.1 (± 0.2) (µg/ml) have the lowest EC50.

Among the compounds that reported EC50 in µM/L units were 7â- hydroxydeoxycryptojaponol (EC50 = 1.15 µM/L), 8α-hydroxyabieta, 9 (11), 13-dien-12-one (EC50 = 1.47), 3α -12Diacetoxyabieta-6,8,11,13-tetraen (EC50 = 1.57) and Savinin (EC50 = 1.13) showed the lowest EC50. Silvestrol (EC50HCOV = 0.003 µM/L, EC50MERS-COV-2 = 0.0013 µM/L) showed the lowest EC50 among the compounds that affected H-COV and MERS-COV-2. Among the compounds acting on the PEDV strain, Oleanane triterpenes8 (EC50 = 0.06 ± 0.02 (µM/L) showed the lowest EC50 (Table 2).

Quality control

Quality control of 36 articles was reviewed using 20 items (Table 3). Study design features that help reduce bias, such as randomization, blindness of the test taker, reason for removing samples, how to select sample size, adjustments for multiple comparisons, similarity of variance between groups, cell authentication and cell contamination, cell strain confirmation, estimate of variation is reported within each group of data, and similarity of variance between the compared groups have not been reported in the literature. Only 52% of the articles reported the item "t or z test reported as one sided or two sided".

Table 3 Articles score based on Agency for Healthcare Research and Quality’s Methods Guide for Effectiveness of Reviews

All articles have reported the following: the exact sample size, whether the samples represent technical or biological replicates, how many times the experiment shown was replicated, the summary estimates are defined as a median or average, the error bars are defined as s.d., s.e.m. or c.i., Common statistical test, or the test is described, the statistical test results are presented, the authors show that their data meet the assumptions of the tests and the source of cell lines.

Virus inhibition

The effect of herbal compound on the virus inhibition showed (Fig. 3) that Saikosaponins B2 (SMD = 293.4; 95% CI 90.08–496.72), Saikosaponins D, Caffeic acid, and S. cusia extract inhibit virus growth more than other compounds. Subgroup studies was performed to find the source of heterogeneity among studies (I2 = 75.9, p < 0.0001).

Fig. 3
figure 3

Forest plot of virus inhibition from studies

All three factors, including chemical structure, virus strain, and host cell type, are heterogeneous agents. We subgrouped the data based on chemical structure into groups of phenolic compounds (9 experiment), alkaloids (2 experiment) and plant extracts (6 experiment) (Table 4). Antiviral effect on alkaloid compounds 80.78% (ES = 80.78; 95% CI 41.14 to 120.41; < 0.0001), phenolic compounds (ES = 44.85; 95% CI 26.17 to 63.53; < 0.0001), and extracts (ES = 14.59; 95% CI 7.96–21.22; < 0.0001) decreases, respectively.

Table 4 Results of subgroup analysis based on various variables for virus titer outcome

If the data were grouped by virus strain, the effect of plant compounds on HCoV (ES = 71.92; 95% CI 46.63–97.21; < 0.0001) was greater than that of SARS-COV-2 strains (ES = 15.81; 95% CI5.44) to 26.19; p = 0.003) and SARS-COV (ES = 12.92; 95% CI 6.38–19.46; < 0.0001). In data grouping by cell type, the effect of plant compounds on cells of human origin (ES = 109.98; 95% CI 45.53–174.43; < 0.001) was greater than that of cells of monkey origin (ES = 23.70; 95% CI 15.07–32.33; < 0.0001).

Virus titer

Virus titer analysis after treatment with herbal medicine in 10 articles and 20 studies showed (Fig. 4) that Trypthantrin (SMD = − 43.40; 95% CI − 73.52 to − 13.28), Sambucus extract, S. cusia extract, Boceprevir, Urtica dioica agglutinin, Indigole B, Hydroxytyrosol aqueus olive pulp, Caffeic acid, Griffithsin, Gallic acid had the most effects on reducing the virus titer, respectively. The effect of the other compounds is shown in the Fig. 4. Heterogeneity of studies was 81.9% I2 = 81.9%, p < 0.0001).

Fig. 4
figure 4

Forest chart for studies that measured virus titers

The data was grouped based on the chemical structure into groups of phenolic compounds, alkaloids, peptides and lectins. The effect of alkaloid compounds (ES = − 27.18; 95% CI − 48.84 to − 5.39; 0.014), extract Plant (ES = − 21.83; 95% CI − 37.83 to − 5.84; 0.007), Lectin compounds (ES = − 18.36; 95% CI − 26.60 to − 10.88; < 0.0001), Peptide compounds (ES = − 10.235; 95% CI − 14.73 to − 5.74; < 0.0001) and phenolic compounds (ES = − 7.40; 95% CI − 10.81 to − 3.97; < 0.0001) decrease on virus titer, respectively.

The data was grouped by virus strain, the effect of plant compounds on HCoV strains (ES = − 17.00; 95% CI − 23.36 to − 10.64; p < 0.0001) is greater than that of other strains on the SARS-COV strain. − 2 (ES = − 9.70; 95% CI − 14.23 to − 5.175; p < 0.0001) and the MERS-COV-2 strain (ES = − 10.50; 95% CI − 18.91 to − 2.10; p = 0.014) are approximately equal. If the data grouped according to the type of host cell, the effect of compounds on the cells of monkey origin (ES = − 15.22; 95% CI − 20.31 to − 10.13; < 0.0001 have a greater effect compared to the cells of human origin (ES = − 8.96; 95% CI − 12.56 to − 5.35; < 0.0001).


According to the SI index, Silvestrol had the greatest effect on the coronavirus family. Among the compounds whose effects on SARS-COV-2 were investigated, Andrographolide (Fig. 5A) had the highest effect. Andrographolide is a diterpene lactone in the isoprenoid family, which is recognized for its broad-spectrum antiviral activity [46]. In silico studies predicted Andrographolide has a potent anti-SARS-COV-2 activity through specific aiming of the host ACE2 receptor and viral factors, such as RNA-dependent RNA polymerase, main protease, 3-CL protease, PL protease, and spike protein [16, 21, 44]. Recently, Shi et al. demonstrated an inhibitory effect of Andrographolide against SARS-COV-2 main protease (Mpro) [47].

Fig. 5
figure 5

Structure of Andrographolide, Lectin, Saikosaponin B2, Tryptanthrin

Based on the EC50 index, Lectin (Fig. 5B), Griffithsin and 7a-hydroxydeoxycryptojaponol showed the lowest levels. Plant lectins have significant antiviral properties against coronaviruses and are non-toxic for host cells. The strongest anti-coronavirus activity was found predominantly among the mannose-binding lectins. The first target in the replication cycle of SARS-COV is located in probably viral attachment, and the second target is at the end of the infectious virus cycle [20]. Lectins are the sparkle of hope for fighting coronaviruses and the worldwide COVID 19 [1].

The results of meta-analysis of inhibiting the growth of the virus after treatment with herbal medicine showed that among the herbal compounds, the antiviral effect of the alkaloid compound Saikosaponin B2 (Fig. 5C) is the most. Saikosaponin B2 showed strong potent anti-coronaviral activity and its method of action probably involves interference in the early stage of viral replication, such as virus uptake and penetration [9]. The results of the virus titer also confirmed Tryptanthrin alkaloid compound (Fig. 5D) as the strongest antiviral effect. Tryptanthrin prevented the both early and the late stages of coronaviral replication, principally by blocking viral RNA genome synthesis and Papain-like protease2 activity [48].

Studies by other researchers have shown that alkaloids, as one of the most widely used natural compounds, can be an effective treatment against SARS-COV-2 due to their simultaneous effects on several therapeutic targets with prominent antiviral effects [34].


Due to the multiplicity of study methods, definitive conclusions are not possible. However, in this study, we tried to gather all available evidence on the effect of plant compounds on SARS-COV-2 to be used for the development and use of promising antiviral agents against SARS-COV-2 and other coronaviruses.

According to the SI results, Silvesterol had the greatest effect on the coronavirus family and Andrographolide had the greatest effect on SARS-COV-2. Based on the EC50, Lectin, Griffithsin and 7a-hydroxydeoxycryptojaponol showed the lowest levels. The results of meta-analysis confirmed the growth inhibition of Saikosaponin B2 and the virus titer results confirmed the alkaloid compound Tryptanthrin as the strongest antiviral molecule. The small number of studies that used alkaloid was one of the limitations of this study and it is suggested to investigate the effect of more alkaloid compounds on coronavirus.

Availability of data and materials

Data are available from corresponding author (FR) by reasonable request.


  1. Abbas HS, K M. Lectins are the sparkle of hope for combating coronaviruses and the global COVID 19. Adv Pharm Bull. 2021.

  2. Alagu Lakshmi S, Shafreen RMB, Priya A, Shunmugiah KP. Ethnomedicines of Indian origin for combating COVID-19 infection by hampering the viral replication: using structure-based drug discovery approach. J Biomol Struct Dyn. 2021;39:4594–609.

    Article  CAS  PubMed  Google Scholar 

  3. Anand U, Jacobo-Herrera N, Altemimi A, Lakhssassi N. A comprehensive review on medicinal plants as antimicrobial therapeutics: Potential avenues of biocompatible drug discovery. Metabolites. 2019;9:1–13.

    Article  CAS  Google Scholar 

  4. Awouafack MD, McGaw LJ, Gottfried S, Mbouangouere R, Tane P, Spiteller M, Eloff JN. Antimicrobial activity and cytotoxicity of the ethanol extract, fractions and eight compounds isolated from Eriosema robustum (Fabaceae). BMC Complement Altern Med. 2013.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Boopathi S, Poma AB, Kolandaivel P. Novel 2019 coronavirus structure, mechanism of action, antiviral drug promises and rule out against its treatment. J Biomol Struct Dyn. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cao R, Hu H, Li Y, Wang X, Xu M, Liu J, Zhang H, Yan Y, Zhao L, Li W, Zhang T, Xiao D, Guo X, Li Y, Yang J, Hu Z, Wang M, Zhong W. Anti-SARS-CoV-2 potential of artemisinins in vitro. ACS Infect Dis. 2020;6:2524–31.

    Article  CAS  PubMed  Google Scholar 

  7. Chen C-J, Michaelis M, Hsu H-K, Tsai C-C, Yang KD, Wu Y-C, Cinatl J, Doerr HW. Toona sinensis Roem tender leaf extract inhibits SARS coronavirus replication. J Ethnopharmacol. 2008;120:108–11.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Chen C, Zuckerman DM, Brantley S, Sharpe M, Childress K, Hoiczyk E, Pendleton AR. Sambucus nigra extracts inhibit infectious bronchitis virus at an early point during replication. BMC Vet Res. 2014.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Cheng PW, Ng LT, Chiang LC, Lin CC. Antiviral effects of saikosaponins on human coronavirus 229E in vitro. Clin Exp Pharmacol Physiol. 2006;33:612–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Choy K-T, Wong AY-L, Kaewpreedee P, Sia SF, Chen D, Hui KPY, Chu DKW, Chan MCW, Cheung PP-H, Huang X, Peiris M, Yen H-L. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020;178:104786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cinatl J, Morgenstern B, Bauer G, Chandra P, Rabenau H, Doerr H. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet. 2003;361:2045–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. D’Amelia V, Docimo T, Crocoll C, Rigano MM. Specialized metabolites and valuable molecules in crop and medicinal plants: the evolution of their use and strategies for their production. Genes (Basel). 2021.

    Article  Google Scholar 

  13. Demeke CA, Woldeyohanins AE, Kifle ZD. Herbal medicine use for the management of COVID-19: a review article. Metab Open. 2021;12:100141.

    Article  CAS  Google Scholar 

  14. Du HZ, Hou XY, Miao YH, Huang BS, Liu DH. Traditional Chinese Medicine: an effective treatment for 2019 novel coronavirus pneumonia (NCP). Chin J Nat Med. 2020;18:206–10.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Du L, Yang Y, Zhou Y, Lu L, Li F, Jiang S. MERS-CoV spike protein : a key target for antivirals. 2017.

  16. Enmozhi SK, Raja K, Sebastine I, Joseph J. Andrographolide as a potential inhibitor of SARS-CoV-2 main protease: an in silico approach. J Biomol Struct Dyn. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Huang Y, Yang C, Xu, Xu W, Liu S X. Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19. Acta Pharmacol Sin. 2020;41:1141–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Janzadeh A, Hamblin MR, Janzadeh N, Arzani H, MahsaTashakori-Miyanroudi YM, Ramezani F. The toxic effect of silver nanoparticles on nerve cells: a systematic review and meta-analysis. Rev Environ Contam Toxicol. 2021;257:93–119.

    Article  PubMed  Google Scholar 

  19. Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, Fang C, Huang D, Huang LQ, Huang Q, Han Y, Hu B, Hu F, Li BH, Li YR, Liang K, Lin LK, Luo LS, Ma J, Ma LL, Peng ZY, Pan YB, Pan ZY, Ren XQ, Sun HM, Wang Y, Wang YY, Weng H, Wei CJ, Wu DF, Xia J, Xiong Y, Xu HB, Yao XM, Ye TS, Yuan YF, Zhang XC, Zhang YW, Zhang YG, Zhang HM, Zhao Y, Zhao MJ, Zi H, Zeng XT, Wang YY, Wang XH. A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Med J Chinese People’s Lib Army. 2020;45:1–20.

    Article  CAS  Google Scholar 

  20. Keyaerts E, Vijgen L, Pannecouque C, Van Damme E, Peumans W, Egberink H, Balzarini J, Van Ranst M. Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle. Antiviral Res. 2007;75:179–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kim D, Min J, Jang M, Lee J, Shin Y, Park C, Song J, Kim H, Kim S, Jin Y-H, Kwon S. Natural bis-benzylisoquinoline alkaloids-tetrandrine, fangchinoline, and cepharanthine, inhibit human coronavirus OC43 Infection of MRC-5 human lung cells. Biomolecules. 2019;9:696.

    Article  CAS  PubMed Central  Google Scholar 

  22. Kumaki Y, Wandersee MK, Smith AJ, Zhou Y, Simmons G, Nelson NM, Bailey KW, Vest ZG, Li JKK, Chan PK-S, Smee DF, Barnard DL. Inhibition of severe acute respiratory syndrome coronavirus replication in a lethal SARS-CoV BALB/c mouse model by stinging nettle lectin, Urtica dioica agglutinin. Antiviral Res. 2011;90:22–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lelešius R, Karpovaite A, Mickiene R, Drevinskas T, Tiso N, Ragažinskiene O, Kubiliene L, Maruška A, Šalomskas A. In vitro antiviral activity of fifteen plant extracts against avian infectious bronchitis virus. BMC Vet Res. 2019;15:1–10.

    Article  Google Scholar 

  24. Li Q, Yi D, Lei X, Zhao J, Zhang Y, Cui X, Xiao X, Jiao T, Dong X, Zhao X, Zeng H, Liang C, Ren L, Guo F, Li X, Wang J, Cen S. Corilagin inhibits SARS-CoV-2 replication by targeting viral RNA-dependent RNA polymerase. Acta Pharm Sin B. 2021.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Li SY, Chen C, Zhang HQ, Guo HY, Wang H, Wang L, Zhang X, Hua SN, Yu J, Xiao PG, Li RS, Tan X. Identification of natural compounds with antiviral activities against SARS-associated coronavirus. Antiviral Res. 2005;67:18–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liang J, Chen J, Tan Z, Peng J, Zheng X, Nishiura K, Ng J, Wang Z, Wang D, Chen Z, Liu L. Extracts of the medicinal herb Sanguisorba officinalis inhibit the entry of human immunodeficiency virus-1. J Food Drug Anal. 2013;21:S52–8.

    Article  PubMed Central  Google Scholar 

  27. Lim XY, Teh BP, Tan TYC. Medicinal Plants in COVID-19: Potential and Limitations. Front Pharmacol. 2021;12:1–8.

    Article  CAS  Google Scholar 

  28. Liu Y, Eaton ED, Wills TE, McCann SK, Antonic A, Howells DW. Human ischaemic cascade studies using SH-SY5Y cells: a systematic review and meta-analysis. Transl Stroke Res. 2018;9:564–74.

    Article  Google Scholar 

  29. Loizzo MR, Saab AM, Tundis R, Statti GA, Menichini F, Lampronti I, Gambari R, Cinatl J, Doerr HW. Phytochemical analysis and in vitro antiviral activities of the essential oils of Seven Lebanon Species. Chem Biodivers. 2008;5:461–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lu H. Drug treatment options for the 2019-new coronavirus (2019- nCoV). Biosci Trends. 2020;14:69–71.

    Article  CAS  PubMed  Google Scholar 

  31. Ma Q, Li R, Pan W, Huang W, Liu B, Xie Y, Wang Z, Li C, Jiang H, Huang J, Shi Y, Dai J, Zheng K, Li X, Hui M, Fu L, Yang Z. Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway. Phytomedicine. 2020;78:153296.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ma Q, Pan W, Li R, Liu B, Li C, Xie Y, Wang Z, Zhao J, Jiang H, Huang J, Shi Y, Dai J, Zheng K, Li X, Yang Z. Liu Shen capsule shows antiviral and anti-inflammatory abilities against novel coronavirus SARS-CoV-2 via suppression of NF-κB signaling pathway. Pharmacol Res. 2020;158:104850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Majlesi Z, Ramezani M, Gerami M (2018) Investigation on some main glycosides content of Stevia rebaudian B . under different concentration of commercial and synthesized silver nanoparticles

  34. Majnooni MB, Fakhri S, Bahrami G, Naseri M, Farzaei MH, Echeverría J. Alkaloids as potential phytochemicals against SARS-CoV-2: approaches to the associated pivotal mechanisms. Evid-Based Complement Altern Med. 2021.

    Article  Google Scholar 

  35. Michaelis M, Doerr HW, Cinatl J. Investigation of the influence of EPs® 7630, a herbal drug preparation from Pelargonium sidoides, on replication of a broad panel of respiratory viruses. Phytomedicine. 2011;18:384–6.

    Article  PubMed  Google Scholar 

  36. Millet JK, Séron K, Labitt RN, Danneels A, Palmer KE, Whittaker GR, Dubuisson J, Belouzard S. Middle East respiratory syndrome coronavirus infection is inhibited by griffithsin. Antiviral Res. 2016;133:1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Müller C, Schulte FW, Lange-Grünweller K, Obermann W, Madhugiri R, Pleschka S, Ziebuhr J, Hartmann RK, Grünweller A. Broad-spectrum antiviral activity of the eIF4A inhibitor silvestrol against corona- and picornaviruses. Antiviral Res. 2018;150:123–9.

    Article  CAS  PubMed  Google Scholar 

  38. O’Keefe BR, Giomarelli B, Barnard DL, Shenoy SR, Chan PKS, McMahon JB, Palmer KE, Barnett BW, Meyerholz DK, Wohlford-Lenane CL, McCray PB. Broad-spectrum in vitro activity and in vivo efficacy of the antiviral protein Griffithsin against emerging viruses of the family Coronaviridae. J Virol. 2010;84:2511–21.

    Article  CAS  PubMed  Google Scholar 

  39. Panyod S, Ho CT, Sheen LY. Dietary therapy and herbal medicine for COVID-19 prevention: a review and perspective. J Tradit Complement Med. 2020;10:420–7.

    Article  Google Scholar 

  40. Prevention I, Biology M, Smit JM, Prevention I (2021) Resveratrol and Pterostilbene potently inhibit SARS-COV-2 replication In vitro.

  41. Ramezani M, Asghari S, Gerami M, Ramezani F, Karimi Abdolmaleki M. Effect of silver nanoparticle treatment on the expression of key genes involved in glycosides biosynthetic pathway in Stevia rebaudiana B. Plant Sugar Tech. 2020;22:518–27.

    Article  CAS  Google Scholar 

  42. Ramezani M, Rajabnia R. Study of environment temperature effect on the antibacterial activity of water extract of different organs of Viola odorata in the different stages of growth. 2017.

  43. Ramezani M, Ramezani F, Gerami M. Nanoparticles in pest incidences and plant disease control. Nanotechnol Agric Crop Prod Prot. 2019.

    Article  Google Scholar 

  44. Rehan M, Ahmed F, Howladar SM, Refai MY, Baeissa HM, Zughaibi TA, Kedwa KM, Jamal MS. A computational approach identified andrographolide as a potential drug for suppressing COVID-19-induced cytokine storm. Front Immunol. 2021;12:1–10.

    Article  CAS  Google Scholar 

  45. Roshdy WH, Rashed HA, Kandeil A, Mostafa A, Moatasim Y, Kutkat O, Abo Shama NM, Gomaa MR, El-Sayed IH, El Guindy NM, Naguib A, Kayali G, Ali MA. EGYVIR: an immunomodulatory herbal extract with potent antiviral activity against SARS-CoV-2. PLoS ONE. 2020;15:1–20.

    Article  CAS  Google Scholar 

  46. Sa-Ngiamsuntorn K, Suksatu A, Pewkliang Y, Thongsri P, Kanjanasirirat P, Manopwisedjaroen S, Charoensutthivarakul S, Wongtrakoongate P, Pitiporn S, Khemawoot P, Chutipongtanate S, Borwornpinyo S, Thitithanyanont A, Hongeng S. Anti-SARS-CoV-2 activity of Andrographis paniculata extract and its major component Andrographolide in human lung epithelial cells and cytotoxicity evaluation in major organ cell representatives. 2020.

  47. Shi T, Huang Y, Chen C, Pi W, Hsu Y. Andrographolide and its fluorescent derivative inhibit the main proteases of 2019-nCoV and SARS-CoV through covalent linkage. 2020.

  48. Tsai YC, Lee CL, Yen HR, Chang YS, Lin YP, Huang SH, Lin CW. Antiviral action of tryptanthrin isolated from strobilanthes cusia leaf against human coronavirus nl63. Biomolecules. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Vellingiri B, Jayaramayya K, Iyer M, Narayanasamy A. COVID-19: A promising cure for the global panic science of the total environment COVID-19: a promising cure for the global panic. Sci Total Environ. 2020;725:138277.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Weathers P. Artemisia annua in vitro A. Artemisia annua. 2021.

    Article  Google Scholar 

  51. Wen C-C, Kuo Y-H, Jan J-T, Liang P-H, Wang S-Y, Liu H-G, Lee C-K, Chang S-T, Kuo C-J, Lee S-S, Hou C-C, Hsiao P-W, Chien S-C, Shyur L-F, Yang N-S. Specific plant terpenoids and lignoids possess potent antiviral activities against severe acute respiratory syndrome coronavirus. J Med Chem. 2007;50:4087–95.

    Article  CAS  PubMed  Google Scholar 

  52. Wen C-C, Shyur L-F, Jan J-T, Liang P-H, Kuo C-J, Arulselvan P, Wu J-B, Kuo S-C, Yang N-S. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Weng J-R, Lin C-S, Lai H-C, Lin Y-P, Wang C-Y, Tsai Y-C, Wu K-C, Huang S-H, Lin C-W. Antiviral activity of Sambucus FormosanaNakai ethanol extract and related phenolic acid constituents against human coronavirus NL63. Virus Res. 2019;273:197767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Xu K, Cai H, Shen Y, Ni Q, Chen Y, Hu S, Li J, Wang H, Yu L, Huang H, Qiu Y, Wei G, Fang Q, Zhou J, Sheng J, Liang T, Li L. [Management of corona virus disease-19 (COVID-19): the Zhejiang experience]. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2020. 49.

  55. Yang J-L, Ha T-K-Q, Dhodary B, Pyo E, Nguyen NH, Cho H, Kim E, Oh WK. Oleanane triterpenes from the flowers of Camellia japonica inhibit porcine epidemic Diarrhea virus (PEDV) replication. J Med Chem. 2015;58:1268–80.

    Article  CAS  PubMed  Google Scholar 

  56. Yang JL, Dhodary B, Quy Ha TK, Kim J, Kim E, Oh WK. Three new coumarins from Saposhnikovia divaricata and their porcine epidemic diarrhea virus (PEDV) inhibitory activity. Tetrahedron. 2015;71:4651–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Yin J, Li G, Li J, Yang Q, Ren X. In vitro and in vivo effects of Houttuynia cordata on infectious bronchitis virus. Avian Pathol. 2011;40:491–8.

    Article  PubMed  Google Scholar 

  58. Zhou J, Li C, Liu X, Chiu MC, Zhao X, Wang D, Wei Y, Lee A, Zhang AJ, Chu H, Cai J, Yip CC, Chan IH, Wong KK, Tsang OT, Chan K, Chan JF, To KK, Chen H, Yuen KY. Infection of bat and human intestinal organoids by SARS-CoV-2. Nat Med. 2020.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Zhuang M, Jiang H, Suzuki Y, Li X, Xiao P, Tanaka T, Ling H, Yang B, Saitoh H, Zhang L, Qin C, Sugamura K, Hattori T. Procyanidins and butanol extract of Cinnamomi Cortex inhibit SARS-CoV infection. Antiviral Res. 2009;82:73–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references


Not applicable


FR was supported by the IRAN University of Medical Sciences, Grant no. P89-F80-U0-N546583.

Author information

Authors and Affiliations



FR: conceptual, methodology, writing, Data screening, Article screening. MM: Data screening. SSH: Data screening. NH: writing, Article screening. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Fatemeh Ramezani.

Ethics declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kesheh, M.M., Shavandi, S., Haeri Moghaddam, N. et al. Effect of herbal compounds on coronavirus; a systematic review and meta-analysis. Virol J 19, 87 (2022).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: