Inhibition of influenza virus internalization by (−)-epigallocatechin-3-gallate

Kim, Meehyein; Kim, Soyeon; Lee, Hye Won; Shin, Jin Soo; Kim, Pilho; Jung, Young‐Sik; Jeong, Hyomin; Hyun, Jaekyung; Lee, Chong-Kyo

doi:10.1016/j.antiviral.2013.08.002

Cited by 117 publications

(79 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EGCG inhibits the infectivity of many unrelated viruses, including important human pathogens (28)(29)(30)(31)(32)(33)(34)(51)(52)(53)(54). Here, we show that EGCG acts directly on virions to inhibit their entry into cells, without affecting the integrity or fluidity of virion envelopes.…”

Section: Discussionmentioning

confidence: 82%

“…EGCG was shown to directly inhibit neuraminidase and viral RNA synthesis (30), as well as to agglutinate virions (37), but only at millimolar concentrations, far higher than the concentrations required to inhibit virion binding. Recently, EGCG was proposed to interfere with IAV fusion, but not adsorption or hemagglutination, by affecting the integrity of the viral envelope (34). In these experiments, IAV virions were not pretreated with EGCG, which is necessary for inhibition of binding and hemagglutination (our data) (30).…”

Section: Discussionmentioning

confidence: 89%

“…They are predominantly comprised of four compounds: epicatechin (EC), epigallocatechin (EGC), epicatechin gallate (ECG), and epigallocatechin gallate (EGCG). EGCG is the most active compound, with activity against human immunodeficiency virus (HIV), influenza A virus (IAV), enterovirus 71, adenovirus (AdV), hepatitis B virus (HBV), clinical isolates of herpes simplex viruses 1 and 2 (HSV-1 and -2), and hepatitis C virus (HCV), among others (27)(28)(29)(30)(31)(32)(33)(34)(35). Derivatives of EGCG, such as digallate dimers, also have antiviral activities (35).…”

mentioning

confidence: 99%

See 2 more Smart Citations

A Small Molecule Inhibits Virion Attachment to Heparan Sulfate- or Sialic Acid-Containing Glycans

Colpitts

Schang

2014

J Virol

128

111

View full text Add to dashboard Cite

Primary attachment to cellular glycans is a critical entry step for most human viruses. Some viruses, such as herpes simplex virus type 1 (HSV-1) and hepatitis C virus (HCV), bind to heparan sulfate, whereas others, such as influenza A virus (IAV), bind to sialic acid. Receptor mimetics that interfere with these interactions are active against viruses that bind to either heparan sulfate or to sialic acid. However, no molecule that inhibits the attachment of viruses in both groups has yet been identified. Epigallocatechin gallate (EGCG), a green tea catechin, is active against many unrelated viruses, including several that bind to heparan sulfate or to sialic acid. We sought to identify the basis for the broad-spectrum activity of EGCG. Here, we show that EGCG inhibits the infectivity of a diverse group of enveloped and nonenveloped human viruses. IMPORTANCEThis study shows that it is possible to develop a small molecule antiviral or microbicide active against the two largest groups of human viruses: those that bind to glycosaminoglycans and those that bind to sialoglycans. This group includes the vast majority of human viruses, including herpes simplex viruses, cytomegalovirus, influenza virus, poxvirus, hepatitis C virus, HIV, and many others.

show abstract

Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

See 1 more Smart Citation

A Small Molecule Inhibits Virion Attachment to Heparan Sulfate- or Sialic Acid-Containing Glycans

Colpitts

Schang

2014

J Virol

128

111

View full text Add to dashboard Cite

show abstract

“…Four sets of vRNP reconstituting plasmids derived from different influenza virus (sub)types were used: 1) four reverse genetics plasmids derived from influenza A/PR/8/34 (encoded pVP-PB1, pVP-PB2, pVP-PA, and pVP-NP, which contain the cDNAs in the bidirectional expression cassette of pHH21), kindly given by M. Kim (Korea Research Institute of Chemical Technology, Daejeon) (Kim et al, 2013); 2) four plasmids derived from the avian influenza A/turkey/England/50-92/1991 (H5N1) virus, containing the cDNA sequences in a pol-II-driven expression cassette, generously given by W. Barclay (Imperial college London, United Kingdom) (Moncorgé et al, 2010; in this set, the PB2 protein contains the avian influenza Glu627 residue); 3) identical to the previous set, with the exception that the PB2-expressing plasmid was mutated to encode the human influenza Lys627 residue (Moncorgé et al, 2010); 4) four reverse genetics plasmids derived from influenza B/Yamanashi/166/98 [designated pAB251-PB1, pAB252-PB2, pAB253-PA, and pAB255-NP, which contain the cDNAs in a bidirectional expression cassette, generously donated by J. McCullers (St. Jude Children's Research Hospital, Memphis, TN) (Hoffmann et al, 2002)]. Set 1 was used in combination with an influenza A-specific firefly luciferase (fluc) reporter plasmid (Kim et al, 2013) that was also given by M. Kim. For sets 2 and 3, the fluc reporter was a kind gift from W. Barclay.…”

Section: Methodsmentioning

confidence: 99%

An Integrated Biological Approach to Guide the Development of Metal-Chelating Inhibitors of Influenza Virus PA Endonuclease

et al. 2014

View full text Add to dashboard Cite

The influenza virus PA endonuclease, which cleaves capped cellular pre-mRNAs to prime viral mRNA synthesis, is a promising target for novel anti-influenza virus therapeutics. The catalytic center of this enzyme resides in the N-terminal part of PA (PA-Nter) and contains two (or possibly one or three) Mg 21 or Mn 21 ions, which are critical for its catalytic function. There is great interest in PA inhibitors that are optimally designed to occupy the active site and chelate the metal ions. We focused here on a series of b-diketo acid (DKA) and DKA-bioisosteric compounds containing different scaffolds, and determined their structure-activity relationship in an enzymatic assay with PA-Nter, in order to build a three-dimensional pharmacophore model. In addition, we developed a molecular beacon (MB)-based PA-Nter assay that enabled us to compare the inhibition of Mn 21 versus Mg 21, the latter probably being the biologically relevant cofactor. This real-time MB assay allowed us to measure the enzyme kinetics of PA-Nter or perform highthroughput screening. Several DKA derivatives were found to cause strong inhibition of PA-Nter, with IC 50 values comparable to that of the prototype L-742,001 (i.e., below 2 mM). Among the different compounds tested, L-742,001 appeared unique in having equal activity against either Mg 21 or Mn 21 . Three compounds (10, with a pyrrole scaffold, and 40 and 41, with an indole scaffold) exhibited moderate antiviral activity in cell culture (EC 99 values 64-95 mM) and were proven to affect viral RNA synthesis. Our approach of integrating complementary enzymatic, cellular, and mechanistic assays should guide ongoing development of improved influenza virus PA inhibitors.

show abstract

“…A recent study by Kim et al has reported the suppressive effects of EGCG on influenza infections, by blocking an early step in the influenza viral life cycle, although it did not have any effect on viral adsorption and viral RNA replication [107]. EGCG was shown to inhibit hemifusion events between viral particles and cellular membrane by reducing the viral membrane integrity suggesting that EGCG may have antiviral effects against enveloped viruses [107]. In accordance to this study, reports of another resent study showed EGCG to act directly on the virions, without having any effects on fluidity or integrity of the envelopes [108].…”

Section: 3 Antimicrobial Properties Of Flavonoidsmentioning

confidence: 99%

Induction of cellular and molecular immunomodulatory pathways by vitamin A and flavonoids

Patel¹,

Vajdy²

2015

Expert Opinion on Biological Therapy

View full text Add to dashboard Cite

Introduction A detailed study of reports on the immunomodulatory properties of vitamin A and select flavonoids may pave the way for using these natural compounds or compounds with similar structures in novel drug and vaccine designs against infectious and autoimmune diseases and cancers. Areas Covered Intracellular transduction pathways, cellular differentiation and functional immunomodulatory responses have been reviewed. The reported studies encompass in vitro, in vivo preclinical and clinical studies that address the role of Vitamin A and select flavonoids in induction of innate and adaptive B and T cell responses, including TH1, TH2 and Treg. Expert Opinion While the immunomodulatory role of vitamin A, and related compounds, is well-established in many preclinical studies, its role in humans has begun to gain wider acceptance. In contrast, the role of flavonoids is mostly controversial in clinical trials, due to the diversity of the various classes of these compounds, and possibly due to the purity and the selected doses of the compounds. However, current preclinical and clinical studies warrant further detailed studies of these promising immuno-modulatory compounds.

show abstract

Inhibition of influenza virus internalization by (−)-epigallocatechin-3-gallate

Cited by 117 publications

References 32 publications

A Small Molecule Inhibits Virion Attachment to Heparan Sulfate- or Sialic Acid-Containing Glycans

A Small Molecule Inhibits Virion Attachment to Heparan Sulfate- or Sialic Acid-Containing Glycans

An Integrated Biological Approach to Guide the Development of Metal-Chelating Inhibitors of Influenza Virus PA Endonuclease

Induction of cellular and molecular immunomodulatory pathways by vitamin A and flavonoids

Contact Info

Product

Resources

About