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dc.contributor.authorLiu, Shufengen_US
dc.contributor.authorWang, Wenyuen_US
dc.contributor.authorBrown, Lauren E.en_US
dc.contributor.authorQiu, Chaoen_US
dc.contributor.authorLajkiewicz, Neilen_US
dc.contributor.authorZhao, Tingen_US
dc.contributor.authorZhou, Jianhuaen_US
dc.contributor.authorPorco, John A.en_US
dc.contributor.authorWang, Tony T.en_US
dc.coverage.spatialNetherlandsen_US
dc.date2015-09-11
dc.date.accessioned2018-01-30T16:52:50Z
dc.date.available2018-01-30T16:52:50Z
dc.date.issued2015-11
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/26870784
dc.identifier.citationShufeng Liu, Wenyu Wang, Lauren E Brown, Chao Qiu, Neil Lajkiewicz, Ting Zhao, Jianhua Zhou, John A Porco, Tony T Wang. 2015. "A Novel Class of Small Molecule Compounds that Inhibit Hepatitis C Virus Infection by Targeting the Prohibitin-CRaf Pathway.." EBioMedicine, Volume 2, Issue 11, pp. 1600 - 1606.
dc.identifier.issn2352-3964
dc.identifier.urihttps://hdl.handle.net/2144/26495
dc.description.abstractIdentification of novel drug targets and affordable therapeutic agents remains a high priority in the fight against chronic hepatitis C virus (HCV) infection. Here, we report that the cellular proteins prohibitin 1 (PHB1) and 2 (PHB2) are pan-genotypic HCV entry factors functioning at a post-binding step. While predominantly found in mitochondria, PHBs localize to the plasma membrane of hepatocytes through their transmembrane domains and interact with both EGFR and CRaf. Targeting PHB by rocaglamide (Roc-A), a natural product that binds PHB1 and 2, reduced cell surface PHB1 and 2, disrupted PHB-CRaf interaction, and inhibited HCV entry at low nanomolar concentrations. A structure-activity analysis of 32 synthetic Roc-A analogs indicated that the chiral, racemic version of aglaroxin C, a natural product biosynthetically related to Roc-A, displayed improved potency and therapeutic index against HCV infection. This study reveals a new class of HCV entry inhibitors that target the PHB1/2-CRaf pathway.en_US
dc.description.sponsorshipGM111625 - NIGMS NIH HHS; R01 DK088787 - NIDDK NIH HHS; P30 CA047904 - NCI NIH HHS; NIH 5P30CA047904-25 - NCI NIH HHS; NIH R01DK088787 - NIDDK NIH HHS; R01 GM073855 - NIGMS NIH HHS; R24 GM111625 - NIGMS NIH HHS; GM073855 - NIGMS NIH HHSen_US
dc.format.extent1600 - 1606en_US
dc.languageeng
dc.relation.ispartofEBioMedicine
dc.rights© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectScience & technologyen_US
dc.subjectLife sciences & biomedicineen_US
dc.subjectMedicine, general & internalen_US
dc.subjectMedicine, research & experimentalen_US
dc.subjectGeneral & internal medicineen_US
dc.subjectResearch & experimental medicineen_US
dc.subjectHCVen_US
dc.subjectEntry factorsen_US
dc.subjectEntry inhibitorsen_US
dc.subjectRocaglatesen_US
dc.subjectMEK-ERK pathwayen_US
dc.subjectEukaryotic translationen_US
dc.subjectReceptor proteinen_US
dc.subjectCD81en_US
dc.subjectRocaglamidesen_US
dc.subjectReplicationen_US
dc.subjectCHIKVppen_US
dc.subjectHCV, hepatitis C virusen_US
dc.subjectHCVcc, cell culture grown HCVen_US
dc.subjectMOI, multiplicity of infectionen_US
dc.subjectPHB, prohibitinen_US
dc.subjectRocaglatesen_US
dc.subjectVSV-Gppen_US
dc.subjectAntiviral agentsen_US
dc.subjectBenzofuransen_US
dc.subjectCell lineen_US
dc.subjectDrug discoveryen_US
dc.subjectHepacivirusen_US
dc.subjectHepatitis Cen_US
dc.subjectHumansen_US
dc.subjectProtein bindingen_US
dc.subjectProto-oncogene oroteins c-rafen_US
dc.subjectRepressor proteinsen_US
dc.subjectSignal transductionen_US
dc.subjectViral envelope proteinsen_US
dc.subjectVirus internalizationen_US
dc.titleA novel class of small molecule compounds that inhibit hepatitis C virus infection by targeting the prohibitin-CRaf pathwayen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.ebiom.2015.09.018
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Arts & Sciencesen_US
pubs.organisational-groupBoston University, College of Arts & Sciences, Department of Chemistryen_US
pubs.publication-statusPublished onlineen_US


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© 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
Except where otherwise noted, this item's license is described as © 2015 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).