EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection
Abstract
:1. Introduction
2. Results
2.1. Inflammation Associated with COVID-19 Pathobiology and Possible Targeting by Catechins
2.1.1. Inflammatory Response in COVID-19 Infection
2.1.2. Targeting Individual Cytokines Might Not Be a Viable Option for COVID-19 Amelioration
2.1.3. EGCG Ameliorates Interleukin-1 (IL-1)-Induced IL-6 Expression
2.2. Initial Cellular Events of COVID-19 and the Role of PLPro
2.2.1. Chronic Inflammatory Response and Cytokine Storm in COVID-19
2.2.2. Cellular Ubiquitination and ISGylation Processes in Infection
2.2.3. PLPro Targets Cellular Ubiquitination and ISGylation Processes
2.2.4. Catechins May Counteract Inhibition of ISGylation/Ubiquitination by PLPro
3. Methods
3.1. Molecular Docking of Catechins on PLPro
3.2. Gene Ontology Studies
3.3. Keywords Searched
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
Disclaimer
Abbreviations
COVID-19 | Coronavirus disease 2019 |
SARS-CoV-2 | severe acute respiratory syndrome coronavirus 2 |
EGCG | epigallocatechin gallate |
PLPro | Papain-like protease |
S protein | SARS-CoV-2 spike glycoprotein |
EC | (−)-epicatechin |
EGC | (−)-epigallocatechin |
Mpro | Main proteinase |
TRAIL | TNF-related apoptosis-inducing ligand |
TNF | Tumor necrosis factor |
M-CSF | macrophage colony-stimulating factor |
GRO-α | Grown regulated oncogene-α |
G-CSF | Granulocyte colony stimulating factor |
IL | Interleukin |
β-NGF | β-Nerve growth factor |
MCP-1 | Monocyte chemoattractant protein-1 |
SCF | Skp1-cullin 1-F-box |
IP-10 | Interferon gamma-induced protein 10 (also known as CXCL10) |
PDGF-BB | Platelet derived growth factor-BB |
IFN | Interferon |
PI3K | Phosphoinositide 3-kinase |
Akt | Protein kinase B |
TNF | Tumor necrosis factor |
CRP | C-Reactive protein |
TIMP1 | Tissue inhibitor of metalloproteinase |
CKM | Creatine Kinase M |
JAK | Janus kinase |
STAT | Signal transducer and activator of transcription protein |
RDS | respiratory distress syndrome |
ACE2 | Angiotensin I Converting Enzyme 2 |
MAPK | Mitogen-activated protein kinase |
TRAF6 | TNF Receptor Associated Factor 6 |
TAK1 | Mitogen-Activated Protein Kinase Kinase Kinase 7 |
NF-κB | Nuclear factor kappa B |
TAM | Tumor-associated macrophage |
MT1-MMP | Membrane type 1-matrix metalloproteinase |
CSF | Colony stimulating factor |
MSCs | Mesenchymal stromal cells |
MIF | macrophage migration inhibitory factor |
AD | Atopic Dermatitis |
SEB | staphylococcal enterotoxin B |
TAC | Transverse aortic constriction |
CXCL | chemokine C-X-C ligand |
NLRP3 | NOD-, LRR- and pyrin domain-containing protein 3 |
SEB | Staphylococcal enterotoxin B |
TLR | Toll-like receptor |
LPS+Aβ | lipopolysaccahride+amyloid β protein |
AT cells | Alveolar type 1 and 2 cells |
DCs | Dendritic cells |
TMPRSS2 | Transmembrane Serine Protease 2 |
ATP | Adenosine triphosphate |
DNA | Deoxyribonucleic acid |
RNA | Ribonucleic acid |
ASC | Apoptosis-associated speck-like protein |
DAMPs | Damage associated molecular patterns |
MIP1α | Macrophage inflammatory protein 1α |
NK cells | Natural killer cells |
UB | Ubiquitin |
ISG | Interferon stimulated gene |
UPS | Ubiquitin proteasome signaling |
RIG-I | Retinoic acid-inducible gene I |
TRIM25 | Tripartite motif-containing protein 25 |
IRF | Interferon regulatory factor |
STING | Stimulator of interferon genes |
TSG101 | Tumor Susceptibility Gene 101 Protein |
PKR | Protein kinase RNA-activated |
CHMP5 | Charged Multivesicular Body Protein 5 |
BECN1 | Beclin 1 |
ERK1 | Mitogen-activated protein kinase 3 |
IFIT1 | Interferon induced protein with tetratricopeptide repeats 1 |
MxA | Myxovirus resistance protein 1 |
p53 | Tumor protein 53 |
PCNA | Proliferating cell nuclear antigen |
HIF1α | Hypoxia-inducible factor 1-alpha |
IQGAP1 | IQ Motif Containing GTPase Activating Protein 1 |
UBC13 | Ubiquitin-conjugating enzyme E2 13 |
UBCH6 | Ubiquitin-conjugating Enzyme H6 |
PP2Cβ | Protein phosphatase 2Cβ |
TRIM25 | Tripartite motif containing 25 |
4EHP | Eukaryotic Translation Initiation Factor 4E Family Member 2 |
PML–RARα | Fusion protein of PML nuclear body scaffold protein and retinoic acid α receptor |
δnp63α | Tumor protein 63 isoform |
Nsp | Non-structural protein |
GCG | (−)-gallocatechingallate |
CG | (−)-catechingallate |
GC | (−)-gallocatechin |
C | (−)-catechin |
References
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Cytokine | Inhibitory Effect of EGCG | Reference |
---|---|---|
TRAIL | Suppresses TRAIL expression levels in auto immune thyroiditis. | [39] |
Sensitizes TRAIL induced apoptosis in ovarian cancer cells, via repression of nuclear factor kappa B (NF-κB) and inhibition of TNF-α and IL-6. | [40] | |
M-CSF | Down regulates M-CSF via miR-16 mediated inhibition of Tumor-associated macrophage (TAM) infiltration and M2 polarization in breast cancer cells. | [41] |
GRO-α | Inhibits GRO-α expression levels by blocking IL-1β mediated stimulation in human Chondrocytes. | [42] |
G-CSF | EGCG is chemopreventive through membrane type 1-matrix metalloproteinase (MT1-MMP) intracellular mediated signaling and sequential activation of the Src and JAK/STAT pathways thus antagonizing concavalin-A-induced colony stimulating factor (CSF)-2 and CSF-3 gene expression in mesenchymal stromal cells (MSCs). | [43] |
IL-6 | Inhibits IL-6 in epithelial ovarian cancer cells. | [44] |
Inhibits IL-6 expression levels by blocking IL-1β mediated stimulation in human chondrocytes. | [42] | |
IL-2 | EGCG exerts anti-inflammatory effect by inhibiting macrophage migration inhibitory factor (MIF) in the pathogenesis of atopic dermatitis (AD). | [44] |
EGCG binds to staphylococcal enterotoxin B (SEB) and neutralizes it in a dose dependent manner and inhibits SEB-induced IL-2 in AD. | [45] | |
β-NGF | EGCG via the PI3K/Akt, glycogen synthase kinase-3 pathway and downstream signaling through cytochrome c and caspase-3 pathways could exert trophic factor effect in neurodegenerative diseases associated with oxidative injury. | [46] |
EGCG significantly exalted NGF-induced neurite outgrowth by increasing the expression levels of mRNA and proteins for the neuronal markers neurofilament-L and growth associated protein-43. | [47] | |
IL-10 | EGCG ameliorated airway inflammation and eosinophil infiltrations in asthmatic mice by increasing the production of IL-10, the number of CD4+CD25+ Foxp3+ Treg cells and expression of Foxp3 mRNA in the lung tissue. | [48] |
MCP-1 | EGCG inhibits MCP-1, by suppressing IL-1β mediated stimulation in human Chondrocytes. | [42] |
SCF | No articles found | |
IL-15 | EGCG regulates effector T cells and naïve T cell population and restores the balance of T helper (Th) cell 17/regulatory T cells, via STAT3 and STAT5. EGCG rescued IL‑7 production and decreased the levels of IL‑15 in transverse aortic constriction (TAC) rats with a therapeutic potential in inhibiting cardiac extracellular matrix remodeling. | [49] |
IL-8 | Inhibits IL-6 expression levels by blocking IL-1β mediated stimulation in human chondrocytes. | [42] |
IL-7 | EGCG suppresses IL-7 signaling by inhibiting the expression of IL-7R and IL-2R receptor subunit (common γ chain) involved in IL-2 mediated T-cell regulation. | [50] |
IP-10 | EGCG reduces airway inflammation via anti-inflammatory mechanism in the airway cells by binding directly to chemokines C-X-C ligand (CXCL)9, CXCL10, and CXCL11, thus limiting their biological activities. | [51] |
PDGF-BB | EGCG, either by plasma membrane incorporated or soluble form, interacts directly with PDGF-BB via the galloyl group in the third position and interferes with PDGF-BB-induced mitogenic signaling pathway by inhibiting tyrosine phosphorylation of the PDGF-Rβ thereby preventing specific receptor binding, inhibiting downstream signal transduction pathways and cell proliferation. | [52] |
IFN-γ | Reduced IFN-γ levels by suppressing NF-κB pathway. | [39] |
EGCG binds to staphylococcal enterotoxin B (SEB) and neutralizes it in a dose dependent manner and inhibits SEB-induced IFN-γ production and IL-2. | [45] | |
IL-18 | EGCG attenuates microglial inflammation and neurotoxicity by suppressing NLRP3 and caspase-11-dependent inflammasome via toll-like receptor (TLR)4/NF-κB pathway in lipopolysaccahride+amyloid β protein (LPS+Aβ)-induced rat primary microglia and hippocampus of APP/PS1 mice by inhibiting the expression of ionised calcium-binding adapter molecule-1, cleaved IL-1β, and cleaved IL-18 induced by LPS+Aβ. | [53] |
EGCG exhibits anti-cancer and anti-atherosclerotic activity by a selective inhibition of the tyrosine phosphorylation of PDGF-Rβ and its downstream signaling pathway. | [54] | |
IL-2rγ | EGCG impacts T-cell regulation by inhibiting IL-2 proprietary α chains resulting in impaired signaling. | [50] |
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Chourasia, M.; Koppula, P.R.; Battu, A.; Ouseph, M.M.; Singh, A.K. EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection. Molecules 2021, 26, 1200. https://doi.org/10.3390/molecules26051200
Chourasia M, Koppula PR, Battu A, Ouseph MM, Singh AK. EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection. Molecules. 2021; 26(5):1200. https://doi.org/10.3390/molecules26051200
Chicago/Turabian StyleChourasia, Mukesh, Purushotham Reddy Koppula, Aruna Battu, Madhu M. Ouseph, and Anil K. Singh. 2021. "EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection" Molecules 26, no. 5: 1200. https://doi.org/10.3390/molecules26051200