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dc.contributor.authorTodt, Daniel
dc.contributor.authorMoeller, Nora
dc.contributor.authorPraditya, Dimas
dc.contributor.authorKinast, Volker
dc.contributor.authorFriesland, Martina
dc.contributor.authorEngelmann, Michael
dc.contributor.authorVerhoye, Lieven
dc.contributor.authorSayed, Ibrahim M
dc.contributor.authorBehrendt, Patrick
dc.contributor.authorDao Thi, Viet Loan
dc.contributor.authorMeuleman, Philip
dc.contributor.authorSteinmann, Eike
dc.date.accessioned2018-10-12T10:49:42Z
dc.date.available2018-10-12T10:49:42Z
dc.date.issued2018-09-01
dc.identifier.issn1872-9096
dc.identifier.pmid30036559
dc.identifier.doi10.1016/j.antiviral.2018.07.010
dc.identifier.urihttp://hdl.handle.net/10033/621518
dc.description.abstractHepatitis E virus (HEV) is the causative agent of hepatitis E in humans and a member of the genus Orthohepevirus in the family Hepeviridae. HEV infections are the common cause of acute hepatitis but can also take chronic courses. Ribavirin is the treatment of choice for most patients and type I interferon (IFN) has been evaluated in a few infected transplantation patients in vivo. However, no effective and specific treatments against HEV infections are currently available. In this study, we evaluated the natural compound silvestrol, isolated from the plant Aglaia foveolata, and known for its specific inhibition of the DEAD-box RNA helicase eIF4A in state-of-the-art HEV experimental model systems. Silvestrol blocked HEV replication of different subgenomic replicons in a dose-dependent manner at low nanomolar concentrations and acted additive to ribavirin (RBV). In addition, HEV p6-based full length replication and production of infectious particles was reduced in the presence of silvestrol. A pangenotypic effect of the compound was further demonstrated with primary isolates from four different human genotypes in HEV infection experiments of hepatocyte-like cells derived from human embryonic and induced pluripotent stem cells. In vivo, HEV RNA levels rapidly declined in the feces of treated mice while no effect was observed in the vehicle treated control animals. In conclusion, silvestrol could be identified as pangenotypic HEV replication inhibitor in vitro with additive effect to RBV and further demonstrated high potency in vivo. The compound therefore may be considered in future treatment strategies of chronic hepatitis E in immunocompromised patients.en_US
dc.rightsAttribution-NonCommercial-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/us/*
dc.subjectAntiviral activityen_US
dc.subjectHepatitis E virus (HEV)en_US
dc.subjectHost targeten_US
dc.subjectHumanized miceen_US
dc.subjectReplicationen_US
dc.subjectSilvestrolen_US
dc.titleThe natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo.en_US
dc.typeArticleen_US
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.en_US
refterms.dateFOA2018-10-12T10:49:43Z
dc.source.journaltitleAntiviral research


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