冠狀病毒Coronavirusl論文-2005 The Adamantane-Derived Bananins Are Potent Inhibitors of the Helicase Activities and Replication of SARS Coronaviru.pdf

冠狀病毒Coronavirusl論文-2005 The Adamantane-Derived Bananins Are Potent Inhibitors of the Helicase Activities and Replication of SARS Coronaviru.pdf

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1、Chemistry&Biology,Vol.12,303311,March,2005,?2005ElsevierLtdAllrightsreserved.DOI10.1016/j.chembiol.2005.01.006TheAdamantane-DerivedBananinsArePotentInhibitorsoftheHelicaseActivitiesandReplicationofSARSCoronavirusJulianA.Tanner,1,6Bo-JianZheng,2,6JieZhou,2mentofParkins

2、onsdisease[4].OtherdrugsincludeRoryM.Watt,1,3Jie-QingJiang,1Kin-LingWong,2rimantadine(againstinfluenzaA)[5],tromantadineYong-PingLin,2Lin-YuLu,1Ming-LiangHe,4(againstherpessimplexvirus),[6]andmemantineHsiang-FuKung,4AndreasJ.Kesel,5,*(N-methyl-D-aspartate[NMDA]recepto

3、rantagonist)[7].andJian-DongHuang1,*Inordertoaddpotentialcytoprotectivefunctionality[8],1DepartmentofBiochemistryoligo-oxa-adamantaneshaverecentlybeenconjugated2DepartmentofMicrobiologytovitaminB6(pyridoxal)tocreateanewclassofada-3DepartmentofChemistryandmantanestheba

4、nanins(Figure1)[9].Wehavesynthe-OpenLaboratoryofChemicalBiologysizedsixbananinderivativesbananin(BAN),iodoba-UniversityofHongKong,Pokfulamnanin(IBN),adeninobananin(ADN),vanillinbananin(VBN),HongKong,Chinaeubananin(EUB),andansabananin(ABN).Thesynthe-4CenterforEmergingI

5、nfectiousDiseasessisofbananinwasdescribed[9],thesynthesisofIBNFacultyofMedicineandADNwillbereportedelsewhere(A.J.K.,submitted),TheChineseUniversityofHongKongandthefinalthreearedescribedinthisreport.HongKong,ChinaSevereacuterespiratorysyndrome(SARS)iscaused5München,Ger

6、manybyinfectionwiththeSARScoronavirus(SCV)[1012].SCVwasrapidlysequencedfollowingitsidentification[13,14],leadingtotherecognitionofanumberofpos-sibledrugtargets.AlthoughtreatmentwithribavirinandSummarycorticosteroidshasbeenshowntohaveaslightposi-tiveeffect[15],side-eff

7、ects[16]andlackofactivityofBananinsareaclassofantiviralcompoundswitharibavirinincellculture[17]highlighttheneedformoreuniquestructuralsignatureincorporatingatrioxa-effectivetreatments.Mostrecentanti-SCVdrugdevel-adamantanemoietycovalentlyboundtoapyridoxalopmenthastarg

8、etedtheviralmainprotease,alsoderivative.Sixmembersofthisclassofcompounds:calledthe3CLprotease,andfollowinganinitialcrystalba

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