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1、AcceptedManuscriptThecardenolideouabainsuppressescoronaviralreplicationviaaugmentingaNa+/K+-ATPase-dependentPI3K_PDK1axissignalingCheng-WeiYang,Hsin-YuChang,Yue-ZhiLee,Hsing-YuHsu,Shiow-JuLeePII:S0041-008X(18)30342-9DOI:doi:10.1016/j.taap.2018.07.028Reference:YTAAP14352Toappea
2、rin:ToxicologyandAppliedPharmacologyReceiveddate:7May2018Reviseddate:10July2018Accepteddate:23July2018Pleasecitethisarticleas:Cheng-WeiYang,Hsin-YuChang,Yue-ZhiLee,Hsing-YuHsu,Shiow-JuLee,ThecardenolideouabainsuppressescoronaviralreplicationviaaugmentingaNa+/K+-ATPase-dependen
3、tPI3K_PDK1axissignaling.Ytaap(2018),doi:10.1016/j.taap.2018.07.028ThisisaPDFfileofanuneditedmanuscriptthathasbeenacceptedforpublication.Asaservicetoourcustomersweareprovidingthisearlyversionofthemanuscript.Themanuscriptwillundergocopyediting,typesetting,andreviewoftheresulting
4、proofbeforeitispublishedinitsfinalform.Pleasenotethatduringtheproductionprocesserrorsmaybediscoveredwhichcouldaffectthecontent,andalllegaldisclaimersthatapplytothejournalpertain.ACCEPTEDMANUSCRIPTThecardenolideouabainsuppressescoronaviralreplicationviaaugmentinga++Na/K-ATPase-
5、dependentPI3K_PDK1axissignaling11111Cheng-WeiYang,Hsin-YuChang,Yue-ZhiLee,Hsing-YuHsu,Shiow-JuLee*1InstituteofBiotechnologyandPharmaceuticalResearch,NationalHealthResearchInstitutes,Miaoli35053,Taiwan,ROC.*Towhomcorrespondenceshouldbeaddressed.Tel:+886-37-246166ext.35715;Fax:+
6、886-37-586456;Email:slee@nhri.org.twACCEPTEDMANUSCRIPTACCEPTEDMANUSCRIPTAbstractCardenolidesareplant-derivedtoxicsubstances.Theircytotoxicityandtheunderlyingmechanisticsignalingaxeshavebeenextensivelydocumented,butonlyafewanti-viralactivitiesofcardenolidesandtheassociatedsigna
7、lingpathwayshavebeenreported.Previously,wereportedthatavarietyofcardenolidesimpartanti-transmissiblegastroenteritiscoronavirus(TGEV)activityinswinetesticular(ST)cells,throughtargetingofthecellmembranesodium/potassiumpump,++Na/K-ATPase.Herein,wefurtherexplorethepotentialsignali
8、ngcascadesassociatedwiththisanti-TGEVactivityinSTcells.Ouabai
