|Year : 2021 | Volume
| Issue : 8 | Page : 327-334
Anti-viral and anti-inflammatory effects of kaempferol and quercetin and COVID-2019: A scoping review
Mohammad Reza Khazdair1, Akbar Anaeigoudari2, Gabriel A Agbor3
1 Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
2 Department of Physiology, Jiroft University of Medical Sciences, Jirof, Iran
3 Center for Research on Medicinal Plants and Traditional Medicine, Institute of Medical Research and Medicinal Plants Studies, Ministry of Scientific Research and Innovations, Yaounde, Cameroon
|Date of Submission||13-Oct-2020|
|Date of Decision||02-Nov-2020|
|Date of Acceptance||12-Mar-2021|
|Date of Web Publication||09-Jul-2021|
Mohammad Reza Khazdair
Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand
Source of Support: None, Conflict of Interest: None
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is a novel coronavirus identified at the end of 2019. It is recognized as the causative agent of coronavirus disease 2019 (COVID-19). Flavonoids have been shown to exhibit therapeutical effect on complications related to COVID-19. The present study reviews possible therapeutic benefits of flavonoids on SARS-CoV-2. The Web of Science, PubMed, Scopus, and Google Scholar were searched using keywords: “COVID-19”, “SARS-CoV-2”, “Kaempferol” and “Quercetin” in the Title/Abstract. Relevant published articles in the English language until August 2020 were considered. Kaempferol and quercetin showed antiviral properties such as inhibition of protein kinase B and phosphorylation of protein kinase and blocking effects on a selective channel (3a channel) expressed in SARS-CoV infected cells. They also reduced the level of reactive oxygen species, expression of inducible nitric oxide synthase, pro-inflammatory mediators including TNF-α, IL-1α, IL-1β, IL-6, IL-10, and IL-12 p70, and chemokines. Kaempferol and quercetin might exert beneficial effects in the control or treatment of COVID-19 because of their antiviral, antioxidant, anti-inflammatory, and immunomodulatory effects.
Keywords: SARS-CoV-2; Flavonoids; Kaempferol; Quercetin; Immunomodulation; Anti-inflammatory; Antiviral effects
|How to cite this article:|
Khazdair MR, Anaeigoudari A, Agbor GA. Anti-viral and anti-inflammatory effects of kaempferol and quercetin and COVID-2019: A scoping review. Asian Pac J Trop Biomed 2021;11:327-34
|How to cite this URL:|
Khazdair MR, Anaeigoudari A, Agbor GA. Anti-viral and anti-inflammatory effects of kaempferol and quercetin and COVID-2019: A scoping review. Asian Pac J Trop Biomed [serial online] 2021 [cited 2021 Aug 2];11:327-34. Available from: https://www.apjtb.org/text.asp?2021/11/8/327/319567
| 1. Introduction|| |
The novel coronavirus (SARS-CoV-2) is an enveloped virus with a single-stranded RNA genome and the third known coronavirus after severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome coronavirus (MERS-CoV). Infection with SARS-CoV-2 leads to severe respiratory disorders and pneumonia-like symptoms in humans. SARS-CoV-2 has high transmissibility and infectivity compared with SARS and MERS. Acute respiratory distress syndrome (ARDS) is the most prevalent cause of death among patients infected with SARS-CoV-2. Cytokine storm is one of the main mechanisms for ARDS. Systemic inflammatory response resulted in release of a large amount of pro-inflammatory mediators and chemokines by immune system in SARS-CoV infection,. The number of CD4+ and CD8+ T cells as humoral responses was significantly reduced in the peripheral blood of patients infected with SARS-CoV-2. Old people and patients with major chronic diseases including cancers, diabetes, and hypertension are at the highest risk of SARS-CoV-2. The receptor-binding domain of SARS-CoV-2 has a great binding affinity to the human angiotensin-converting enzyme 2 (ACE2) receptors, which are widely expressed in various cells including lung, brain, kidney, and digestive tract. Reduction of CD4+ and CD8+ T cells takes place in the acute phase of infection with SARS-CoV.
It has been suggested that the therapeutic options focused on the antiviral agents may alleviate SARS-CoV-2 symptoms as well as reduce the inflammatory responses. Various biological compounds such as flavonoids have been reported to possess antiviral, anti-inflammatory, antioxidant, and other therapeutic properties in nature,. Anti-SARS coronavirus 3C-like protease effects of plant-derived phenolic compounds have also been reported.
The present review article discussed the possible therapeutic action of flavonoids against SARS-CoV-2 in relation to their antiviral and anti-inflammatory activities. The possible therapeutic pathway of kaempferol and quercetin in affecting COVID-19 is shown in [Figure 1].
|Figure 1: Therapeutical pathway of kaempferol and quercetin in treating COVID-19.|
Click here to view
| 2. Methods|| |
In this narrative review, we used different databases such as PubMed, Web of Science, Scopus, and Google scholar to collect information by searching keywords “COVID-19”, “SARS-CoV-2”, “Kaempferol”, and “Quercetin”. In vivo and in vitro studies in the English language until August 2020 were considered. Non-English articles and letters to editor were omitted.
| 3. Kaempferol|| |
Kaempferol is a flavonoid extracted from the medicinal herb Kaempferol galanga L, Crocus sativus, Portulaca oleracea, and some other plants. This compound was found in concentrations ranging from 0.625 to 5 μg/mL in the extract of plants. Anti-inflammatory and immunomodulatory effects of kaempferol have been suggested. Pharmacological effects of kaempferol including antioxidant, anti-inflammatory, anti-cancer, and anti-microbe properties were also reported,.
3.1. Antiviral effects of kaempferol
Based on research results, kaempferol was shown to suppress the activity of influenza viruses such as H1N1 and H9N2 and hepatitis B virus in vitro studies. Other results reported kaempferol at a very low concentration (12.6 μM) exhibited an anti-Japanese encephalitis virus effect. This effect was mediated through the inhibition of viral replication and protein synthesis. Inhibition of enterovirus 71 replication and the activity of internal ribosome entry site by FUBP and HNRP have been documented by kaempferol.
In an in vitro study, H9N2 influenza virus-infected MH-S cells were treated with kaempferol (50 mM) and it significantly reduced ROS, malondialdehyde, TNF-α, IL-1β, and IL-6 accumulation. Moreover, kaempferol remarkably inhibited the upregulation of tolllike receptor 4, phosphorylation level of IκB-α and nuclear factor-κB (NF-κB) p65, myeloid differentiation factor 88, NF-κB p65 DNA binding activity, and phosphorylation level of mitogen-actived protein kinases (MAPKs).
Kaempferol at dose 100 μmol/L completely inhibited bovine herpesvirus 1 replication in Madin-Darby bovine kidney cells. It also affects the viral replication at the post-entry stages. Kaempferol showed potent antiviral properties due to inhibition of protein kinase B (Akt) signaling. The anti-HIV-1 activities of flavonoids, kaempferol, and kaempferol-7-O-glucoside (10-100 μg/mL) have been reported.
The potency of kaempferol for blocking a cation-selective channel that is expressed in the infected cell (3a channel) of SARS-CoV has been shown. Kaempferol (20 μM) blocked more than 50% of these channels. In an in vivo study, kaempferol (15 mg/kg, i.g.) reduced pulmonary edema, lung wet/dry weight, myeloperoxidase activity, pulmonary capillary permeability, and the number of inflammatory cells in BALB/C mice intranasally infected with H9N2 influenza virus. Kaempferol also reduced production of TNF-α, IL-1β, and IL-6, and decreased ROS activity and production of malondialdehyde, while increasing the superoxide dismutase activity. Antiviral effects of kaempferol are summarized in [Table 1].
3.2. Anti-inflammatory effects of kaempferol
Kaempferol (25 and 50 μmol/L) significantly reduced the expression of TNF-α, IL-8, and macrophage inflammatory protein 1 alpha (MIP-1a) in human promonocytic U937 cells-derived macrophages (dU937).
Treatment with kaempferol (100 μM) significantly increased forkhead box P3 (FOXP3), a protein-coding gene expressed in Treg cells. Furthermore, kaempferol amplified mRNA levels of FOXP3 and IL-10 in Treg cells. These results suggested that kaempferol may potentially be used for the treatment of autoimmune diseases. The mRNA expression of matrix metalloproteinase-2 was suppressed by kaempferol (20, 40, 60, 80, and 100 μM). In addition, it inhibited the migration of cancer cells in a dose-dependent manner.
Kaempferol (20 μM) suppressed histamine and β-hexosaminidase secretion and reduced the expression of IL-4 and TNF-α at mRNA and protein levels in IgE-sensitized RBL-2H3 cells. It also inhibited P38 mitogen-activated protein kinases in the cells.
Adminstration of kaempferol (30 and 150 mg/kg, p.o.) reduced serum levels of TNF-α and IL-1β in rabbits fed with a high-cholesterol diet. Furthermore, kaempferol down-regulated mRNA and protein expression of inflammatory mediators including E-selectin, intercellular adhesion molecule-1 (ICAM-1), and MCP-1 in the aorta of rabbits. Therefore, kaempferol modulates the expression of inflammatory molecules at gene and protein levels and exerts anti-inflammatory activities.
Kaempferol administration was found to modulate allergic airway disease in ovalbumin-sensitized mice. Subcutaneous administration of kaempferol (3, 30 and 100 mg/kg) decreased the levels of IL-5 and IL-13 (especially at 100 mg/kg) in the bronchoalveolar lavage fluid (BALF) and its effect was comparable to that of dexamethasone (1 mg/kg). Additionally, the expressions of cell markers (CD4+, B220+, MHC class II, and CD40 molecule) in BALF cells were decreased by kaempferol. Treatment with kaempferol before or after the establishment of allergic disease down-regulated Th2 cytokines.
Oral administration of kaempferol (50 mg/kg) significantly inhibited the antigen-induced passive cutaneous anaphylaxis response in IgE-sensitized mice. Treatment of aged rats with kaempferol (2 or 4 mg/kg/day) inhibited NF-κB function by inhibiting the activation of nuclear factor-inducing kinase/IκB kinase and MAPKs signal pathways in rat kidney. The anti-inflammatory properties of kaempferol are shown in [Table 2].
| 4. Quercetin|| |
Quercetin is a natural polyphenolic flavonoid with antioxidant, anticancer, and antiviral properties found in many plants such as Portulaca oleracea and Allium cepa. Anti-inflammatory and anti-asthmatic effects of this agent were also reported. Pharmacological effects of quercetin including vasodilation and anti-microbe effects have been reported. The immunoregulatory function of quercetin on dendritic cells (DCs) through suppressing the expression of CD40, CD80, and CD86 in lipopolysaccharide (LPS)-stimulated DCs has been shown.
4.1. Antiviral effects of quercetin
3-Methyquercetin could inhibit poliovirus by blocking RNA synthesis. Quercetin also inhibits rhinovirus infection via suppression of replication. This plant flavonoid has also been demonstrated to stop the chikungunya virus infection via inhibition of heat shock protein 70 serving as a receptor for this virus. Quercetin along with apigenin and isorhamnetin inhibited the hepatitis C virus’s life cycle. This effect is attributed to put off viral genome replication and affect infectious particles’ morphogenesis. Quercetin has been suggested to inhibit murine coronavirus and dengue virus in vitro. Quercetin administration has been shown to be effective in the treatment of SARS-CoV2 via acting on caspase 3, MAPK1 and NF-κB signaling pathways to suppress the elevated cytokine levels. Quercetin has been reported to block the binding sites on the superficial spikes of the SARS-CoV2 and to prevent the spread of the virus. The ability of quercetin to inhibit the main protease (3Clpro) from MERS-CoV and SARS-CoV2 has been also documented. Alteration of human genes encoding proteins targeted by SARS-CoV2 is also attributed to quercetin.
In silico modeling showed that quercetin as potential highly effective disruptors of the initial infection process attaches to the interface between the SARS-CoV-2 viral spike protein and the epithelial cell ACE2 protein.
The results of a study showed that quercetin and kaempferol presented in Ficus benjamina leaves inhibited herpes simplex virus I. Quercetin along with kaempferol has been proposed to bind the proteins of SARS-CoV2 which is involved in inflammatory responses and modulation of immune system. They could affect the expression of cyclooxygenase 2, interleukins, MAPKs and alter the signaling cascade related to toll-like receptors and JAK-STAT pathway,. According to scientific evidence, quercetin and kaempferol derived from Huoxiang zhengqi could inactive SARS-CoV2. This antiviral effect is associated with the inhibition of the replication of SARS-CoV2 by affecting PI3K-Akt signaling pathway. It is also predicted that quercetin and kaempferol have a high affinity for SARS-CoV2 3CL hydrolase. These two flavonoids can join to ACE2 and affect intracellular signaling cascades including Bcl-2, PTGS2, and caspase 3 for inhibiting viral infection resulting from hepatitis C, herpesvirus, measles, and Epstein-Barr virus. The antiviral effects of quercetin are summarized in [Table 3].
4.2. Anti-inflammatory effects of quercetin
Pharmacological properties of quercetin such as antioxidant, anticancer, and antiviral effects have been reported. Quercetin (0.5-50 μM) increased gene expression and production of IFN-γ, but down-regulated the production of IL-4 in normal peripheral blood mononuclear cells (1×106 cells/mL). The beneficial effects of quercetin on immune system may be attributed to the induction of Th1-derived cytokines secretion and inhibition of Th2 derived cytokines secretion.
Treatment of LPS-stimulated DCs with quercetin (6.25, 12.5, 50, and 100 μg/mL) inhibited production of TNF-α and impaired production of cytokines and chemokines in a dose-dependent manner. Quercetin also remarkably reduced generation of cytokines (IL-1α, IL-1β, IL-6, IL-10, and IL-12 p70) and chemokines (MCP-1, MIP-1α, and MIP-1β) in stimulated DCs. Furthermore, quercetin significantly suppressed the enhanced expression of CD40, CD80, and CD86 in LPS-stimulated DCs.
Treatment of bone marrow-derived macrophages with quercetin (1, 10, 50 μM) inhibited expression of inducible nitric oxide synthase (iNOS), TNF-α, IL-1β, and IκB-α phosphorylation induced by LPS. Furthermore, administration of quercetin (1 mg/kg/day, p.o.) in rats inhibited production of TNF-α and IL-1β and expression of iNOS induced by dextran sulfate sodium.
Quercetin (8 mg/kg/day, i.p) remarkably reduced the level of eosinophils (68.79%) in BALF of mice challenged with ovalbumin. Quercetin also reduced secretion of IL-4 and IL-5 as well as mRNA expression of MMP-9 and EPO but increased the level of IFN-γ in the BALF of treated mice compared to non-treated mice.
Topical administration of quercetin (0.01%), resveratrol (0.01%), and their combination (0.01%) in desiccating stress mice model of dry eye disease (DED) reduced corneal staining in mice. Quercetin, resveratrol, and combined therapy decreased concentration of IL-1α in tear compared to vehicle treatment. Furthermore, quercetin decremented CD4+ T cells desiccating stress-exposed mice.
The effect of quercetin in rheumatoid arthritis patients was studied. Treatment patients with quercetin (1 500 mg/day, p.o.) plus 100 mg azathioprine for 8 weeks, remarkably decreased the levels of IL-6, C3, and C4, but increased the level of IL-10 compared to the azathioprine plus placebo-treated group. Treatment with azathioprine alone did not significantly affect the level of intercellular adhesion molecule (ICAM-1) while treatment with quercetin significantly reduced ICAM-1 compared to the azathioprine alone-treated group. Oral administration of quercetin in combination with azathioprine produced an immunomodulatory action by reducing the level of IL-6, ICAM-1, and complement proteins while it elevated the serum level of IL-10. The anti-inflammatory effects of carvacrol, another flavonoid on chemical gas exposed patients were also reported.
Kaempferol and quercetin showed antiviral properties via the inhibition of protein kinase B and phosphorylation of protein kinase and blockage of effects on a selective channel that is expressed in the infected cell by SARS-CoV (3a channel). They also reduced the level of ROS, expression of iNOS, pro-inflammatory cytokines including TNF-α, IL-1α, IL-1β, IL-6, IL-10, and IL-12 p70, and chemokines. The anti-inflammatory properties of quercetin are shown in [Table 4].
| 5. Conclusion|| |
This review descriptively highlights the possible effects of kaempferol and quercetin with their underlying mechanism(s) of action on COVID-19. According to the literature survey, anti-viral properties of these flavonoids are mediated through the inhibition of protein kinase B and phosphorylation of protein kinase and blocking effects on 3a channel. They also reduced the level of ROS, expression of iNOS, and pro-inflammatory mediators such as TNF-α, IL-1α, IL-1β, IL-6, IL-10, and chemokines.
Kaempferol and quercetin modulated immune responses by reduction of pro-inflammatory mediators such as IL-4, IL-1 β, IL-6, transforming growth factor-β, and IL-17, and enhancement of anti-inflammatory mediators such as IFN-γ and FOXP3. ARDS with cytokine storm of pro-inflammatory cytokines is the main death cause of COVID-19. Therefore, kaempferol and quercetin with anti-inflammatory and immunomodulatory effects may be useful for the treatment of COVID-19. Although, more clinical studies are required to support drug effectiveness.
Conflict of interest statement
We declare that there is no conflict of interest.
MRK was responsible for study design, literature search, prepared and revised the manuscript. AA helped in study design, literature search, and preparation of the manuscript. GAA was responsible for critical review and editing of the manuscript. All the authors approved the final version of the manuscript.
| References|| |
Malik YS, Sircar S, Bhat S, Sharun K, Dhama K, Dadar M, et al. Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments. Veterinar Quarter
Shanmugaraj B, Malla A, Phoolcharoen W. Emergence of novel coronavirus 2019-nCoV: Need for rapid vaccine and biologics development. Pathogens
Liu Y, Gayle AA, Wilder-Smith A, Rocklöv J. The reproductive number of COVID-19 is higher compared to SARS coronavirus. J Travel Med
Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Resp Med
Cameron MJ, Bermejo-Martin JF, Danesh A, Muller MP, Kelvin DJ. Human immunopathogenesis of severe acute respiratory syndrome (SARS). Virus Res
Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet
Lancet T. Redefining vulnerability in the era of COVID-19. Lancet
Madjid M, Safavi-Naeini P, Solomon SD, Vardeny O. Potential effects of coronaviruses on the cardiovascular system: A review. JAMA Cardiol
Fan YY, Huang ZT, Li L, Wu MH, Yu T, Koup RA, et al. Characterization of SARS-CoV-specific memory T cells from recovered individuals 4 years after infection. Arch Virol
Monteleone G, Ardizzone S. Are patients with inflammatory bowel disease at increased risk for Covid-19 infection? J Crohns Colitis
Tapas AR, Sakarkar D, Kakde R. Flavonoids as nutraceuticals: A review. Trop J Pharm Res
Khazdair M, Alavinezhad A, Boskabady M. Carvacrol ameliorates haematological parameters, oxidant/antioxidant biomarkers and pulmonary function tests in patients with sulphur mustard-induced lung disorders: A randomized double-blind clinical trial. J Clin Pharm Therap
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
Okamoto I, Iwaki K, Koya-Miyata S, Tanimoto T, Kohno K, Ikeda M, et al. The flavonoid Kaempferol suppresses the graft-versus-host reaction by inhibiting type 1 cytokine production and CD8+
T cell engraftment. Clin Immunol
Liu Y, Gao L, Guo S, Liu Y, Zhao X, Li R, et al. Kaempferol alleviates angiotensin II-induced cardiac dysfunction and interstitial fibrosis in mice. Cell Physiol Biochem
Kianmehr M, Khazdair MR. Possible therapeutic effects of Crocus sativus
stigma and its petal flavonoid, kaempferol, on respiratory disorders. Pharm Biol
Jeong HJ, Ryu YB, Park SJ, Kim JH, Kwon HJ, Kim JH, et al. Neuraminidase inhibitory activities of flavonols isolated from Rhodiola rosea
roots and their in vitro
anti-influenza viral activities. Bioorgan Med Chem
Li J, Huang H, Feng M, Zhou W, Shi X, Zhou P. In vitro
and in vivo
antihepatitis B virus activities of a plant extract from Geranium carolinianum
L. Antiviral Res
Zhang T, Wu Z, Du J, Hu Y, Liu L, Yang F, et al. Anti-Japanese-encephalitis-viral effects of kaempferol and daidzin and their RNA-binding characteristics. PLoS One
Tsai FJ, Lin CW, Lai CC, Lan YC, Lai CH, Hung CH, et al. Kaempferol inhibits enterovirus 71 replication and internal ribosome entry site (IRES) activity through FUBP and HNRP proteins. Food Chem
Zhang R, Ai X, Duan Y, Xue M, He W, Wang C, et al. Kaempferol ameliorates H9N2 swine influenza virus-induced acute lung injury by inactivation of TLR4/MyD88-mediated NF-κB and MAPK signaling pathways. Biomed Pharmacother
Zhu L, Wang P, Yuan W, Zhu G. Kaempferol inhibited bovine herpesvirus 1 replication and LPS-induced inflammatory response. Acta Virol
Behbahani M, Sayedipour S, Pourazar A, Shanehsazzadeh M. In vitro
anti-HIV-1 activities of kaempferol and kaempferol-7-O
-glucoside isolated from Securigera securidaca. Res Pharm Sci
Schwarz S, Sauter D, Wang K, Zhang R, Sun B, Karioti A, et al. Kaempferol derivatives as antiviral drugs against the 3a channel protein of coronavirus. Planta Med
Lin F, Luo X, Tsun A, Li Z, Li D, Li B. Kaempferol enhances the suppressive function of Treg cells by inhibiting FOXP3 phosphorylation. Int Immunopharmacol
Lin CW, Chen PN, Chen MK, Yang WE, Tang CH, Yang SF, et al. Kaempferol reduces matrix metalloproteinase-2 expression by down-regulating ERK1/2 and the activator protein-1 signaling pathways in oral cancer cells. PLoS One
Kim M, Lim SJ, Kang SW, Um BH, Nho CW. Aceriphyllum rossii
extract and its active compounds, quercetin and kaempferol inhibit IgE-mediated mast cell activation and passive cutaneous anaphylaxis. J Agric Food Chem
Kong L, Luo C, Li X, Zhou Y, He H. The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits. Lipid Health Dis
Medeiros K, Faustino L, Borduchi E, Nascimento R, Silva T, Gomes E, et al. Preventive and curative glycoside kaempferol treatments attenuate the TH2-driven allergic airway disease. Int Immunopharmacol
Park MJ, Lee EK, Heo HS, Kim MS, Sung B, Kim MK, et al. The anti-inflammatory effect of kaempferol in aged kidney tissues: the involvement of nuclear factor-κB via
nuclear factor-inducing kinase/IκB kinase and mitogen-activated protein kinase pathways. J Med Food
Hashemzaei M, Delarami Far A, Yari A, Heravi RE, Tabrizian K, Taghdisi SM, et al. Anticancer and apoptosis-inducing effects of quercetin in vitro
and in vivo. Oncol Rep
Khazdair MR, Anaeigoudari A, Kianmehr M. Anti-asthmatic effects of Portulaca oleracea
and its constituents, a review. J Pharmacopunct
Taguchi K, Tano I, Kaneko N, Matsumoto T, Kobayashi T. Plant polyphenols morin and quercetin rescue nitric oxide production in diabetic mouse aorta through distinct pathways. Biomed Pharmacother
Huang RY, Yu YL, Cheng WC, OuYang CN, Fu E, Chu CL. Immunosuppressive effect of quercetin on dendritic cell activation and function. J Immunol
Castrillo J, Berghe DV, Carrasco L. 3-Methylquercetin is a potent and selective inhibitor of poliovirus RNA synthesis. Virology
Ganesan S, Faris AN, Comstock AT, Wang Q, Nanua S, Hershenson MB, et al. Quercetin inhibits rhinovirus replication in vitro
and in vivo. Antiviral Res
Ghosh A, Desai A, Ravi V, Narayanappa G, Tyagi BK. Chikungunya virus interacts with heat shock cognate 70 protein to facilitate its entry into mosquito cell line. Intervirology
Rojas Á, Del Campo JA, Clement S, Lemasson M, García-Valdecasas M, Gil-Gómez A, et al. Effect of quercetin on hepatitis C virus life cycle: From viral to host targets. Sci Rep
Chiow K, Phoon M, Putti T, Tan BK, Chow VT. Evaluation of antiviral activities of Houttuynia cordata
Thunb. extract, quercetin, quercetrin and cinanserin on murine coronavirus and dengue virus infection. Asian Pac J Trop Med
Sun X, Zhang Y, Liu Y, Wang G. Study on mechanism of reduning injection in treating novel coronavirus pneumonia based on network pharmacology. J Chin Med Mat
Vijayakumar BG, Ramesh D, Joji A, Kannan T. In silico
pharmacokinetic and molecular docking studies of natural flavonoids and synthetic indole chalcones against essential proteins of SARS-CoV-2. Eur J Pharmacol
Abian O, Ortega-Alarcon D, Jimenez-Alesanco A, Ceballos-Laita L, Vega S, Reyburn HT, et al. Structural stability of SARS-CoV-2 3CLpro and identification of quercetin as an inhibitor by experimental screening. Int J Biol Macromol
Glinsky GV. Tripartite combination of candidate pandemic mitigation agents: Vitamin D, quercetin, and estradiol manifest properties of medicinal agents for targeted mitigation of the COVID-19 pandemic defined by genomics-guided tracing of SARS-CoV-2 targets in human cells. Biomedicines
Williamson G, Kerimi A. Testing of natural products in clinical trials targeting the SARS-CoV-2 (Covid-19) viral spike protein-angiotensin converting enzyme-2 (ACE2) interaction. Biochem Pharmacol
Yarmolinsky L, Huleihel M, Zaccai M, Ben-Shabat S. Potent antiviral flavone glycosides from Ficus benjamina
Wang L. Study on the network pharmacology and preliminary evidence of Lianhua Qingwen in the treatment of novel coronavirus (2019-nCoV). J Chin Med Mat
Huang YF, Bai C, He F, Xie Y, Zhou H. Review on the potential action mechanisms of Chinese medicines in treating Coronavirus Disease 2019 (COVID-19). Pharmacol Res
Kong Y, Wu H, Chen Y, Lai S, Yang Z, Chen J. Mechanism of Tanreqing Injection on treatment of coronavirus disease 2019 based on network pharmacology and molecular docking. Chine Trad Herb Drug
Jimilihan S. Study on the active components in the adjuvant treatment of novel coronavirus pneumonia (COVID-19) with Jinhua Qinggan Granules based on network pharmacology and molecular docking. J Chin Med Mat
Nair MP, Kandaswami C, Mahajan S, Chadha KC, Chawda R, Nair H, et al. The flavonoid, quercetin, differentially regulates Th-1 (IFNγ) and Th-2 (IL4) cytokine gene expression by normal peripheral blood mononuclear cells. Biochim Biophys Acta (BBA)-Mol Cell Res
Comalada M, Camuesco D, Sierra S, Ballester I, Xaus J, Gálvez J, et al. In vivo
quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NFκB pathway. Eur J Immunol
Park HJ, Lee CM, Jung ID, Lee JS, Jeong YI, Chang JH, et al. Quercetin regulates Th1/Th2 balance in a murine model of asthma. Int Immunopharmacol
Abengózar-Vela A, Schaumburg CS, Stern ME, Calonge M, Enríquez-de-Salamanca A, González-García MJ. Topical quercetin and resveratrol protect the ocular surface in experimental dry eye disease. Ocul Immunol Inflamm
Al-Rekabi MD, Ali SH, Al-Basaisi H, Hashim F, Hussein AH, Abbas HK. Immunomodulatory effects of quercetin in patient with active rheumatoid arthritis. Br J Med Health Res
Yu ES, Min HJ, An SY, Won HY, Hong JH, Hwang ES. Regulatory mechanisms of IL-2 and IFNγ suppression by quercetin in T helper cells. Biochem Pharmacol
Sternberg Z, Chadha K, Lieberman A, Hojnacki D, Drake A, Zamboni P, et al. Quercetin and interferon-β modulate immune response (s) in peripheral blood mononuclear cells isolated from multiple sclerosis patients. J Neuroimmunol
[Table 1], [Table 2], [Table 3], [Table 4]