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Polyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action

dc.contributor.authorCALLAND, Noemie
dc.contributor.authorSAHUC, Marie-Emmanuelle
dc.contributor.authorBELOUZARD, Sandrine
dc.contributor.authorPENE, Veronique
dc.contributor.authorBONNAFOUS, Pierre
dc.contributor.authorMESALAM, Ahmed Atef
dc.contributor.authorDELOISON, Gaspard
dc.contributor.authorDESCAMPS, Veronique
dc.contributor.authorSAHPAZ, Sevser
dc.contributor.authorWYCHOWSKI, Czeslaw
dc.contributor.authorLAMBERT, Olivier
dc.contributor.authorBRODIN, Priscille
dc.contributor.authorDUVERLIE, Gilles
dc.contributor.authorMEULEMAN, Philip
dc.contributor.authorROSENBERG, Arielle R.
dc.contributor.authorDUBUISSON, Jean
dc.contributor.authorROUILLE, Yves
dc.contributor.authorSERON, Karin
dc.date.accessioned2020-09-03T08:02:18Z
dc.date.available2020-09-03T08:02:18Z
dc.date.issued2015
dc.identifier.issn0022-538X
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/11007
dc.description.abstractEnDespite the validation of direct-acting antivirals for hepatitis C treatment, the discovery of new compounds with different modes of action may still be of importance for the treatment of special patient populations. We recently identified a natural molecule, epigallocatechin-3-gallate (EGCG), as an inhibitor of hepatitis C virus (HCV) targeting the viral particle. The aim of this work was to discover new natural compounds with higher anti-HCV activity than that of EGCG and determine their mode of action. Eight natural molecules with structure similarity to EGCG were selected. HCV JFH1 in cell culture and HCV pseudoparticle systems were used to determine the antiviral activity and mechanism of action of the compounds. We identified delphinidin, a polyphenol belonging to the anthocyanidin family, as a new inhibitor of HCV entry. Delphinidin inhibits HCV entry in a pangenotypic manner by acting directly on the viral particle and impairing its attachment to the cell surface. Importantly, it is also active against HCV in primary human hepatocytes, with no apparent cytotoxicity and in combination with interferon and boceprevir in cell culture. Different approaches showed that neither aggregation nor destruction of the particle occurred. Cryo-transmission electron microscopy observations of HCV pseudoparticles treated with delphinidin or EGCG showed a bulge on particles that was not observed under control conditions. In conclusion, EGCG and delphinidin inhibit HCV entry by a new mechanism, i.e., alteration of the viral particle structure that impairs its attachment to the cell surface. IMPORTANCE In this article, we identify a new inhibitor of hepatitis C virus (HCV) infection, delphinidin, that prevents HCV entry. This natural compound, a plant pigment responsible for the blue-purple color of flowers and berries, belongs to the flavonoid family, like the catechin EGCG, the major component present in green tea extract, which is also an inhibitor of HCV entry. We studied the mode of action of these two compounds against HCV and demonstrated that they both act directly on the virus, inducing a bulging of the viral envelope. This deformation might be responsible for the observed inhibition of virus attachment to the cell surface. The discovery of such HCV inhibitors with an unusual mode of action is important to better characterize the mechanism of HCV entry into hepatocytes and to help develop a new class of HCV entry inhibitors.
dc.language.isoen
dc.title.enPolyphenols Inhibit Hepatitis C Virus Entry by a New Mechanism of Action
dc.typeArticle de revue
dc.identifier.doi10.1128/jvi.01473-15
dc.subject.halChimie/Matériaux
bordeaux.journalJournal of virology
bordeaux.page10053-10063
bordeaux.volume89
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.issue19
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20virology&rft.date=2015&rft.volume=89&rft.issue=19&rft.spage=10053-10063&rft.epage=10053-10063&rft.eissn=0022-538X&rft.issn=0022-538X&rft.au=CALLAND,%20Noemie&SAHUC,%20Marie-Emmanuelle&BELOUZARD,%20Sandrine&PENE,%20Veronique&BONNAFOUS,%20Pierre&rft.genre=article


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