Novel Pandemic Influenza A(H1N1) Viruses Are Potently Inhibited by DAS181, a Sialidase Fusion Protein 英文参考文献.docVIP
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Novel Pandemic Influenza A(H1N1) Viruses Are Potently Inhibited by DAS181, a Sialidase Fusion Protein 英文参考文献
NovelPandemicInfluenzaA(H1N1)VirusesArePotently
InhibitedbyDAS181,aSialidaseFusionProtein
GallenB.Triana-Baltzer1,LarisaV.Gubareva2,JohnM.Nicholls3,MelissaB.Pearce2,VasiliyP.Mishin2,
JessicaA.Belser2,Li-MeiChen2,ReneeW.Y.Chan3,MichaelC.W.Chan3,MariaHedlund1,JeffreyL.
Larson1,RonaldB.Moss1,JacquelineM.Katz2,TerrenceM.Tumpey2,FangFang1*
1NexBio,Inc.,SanDiego,California,UnitedStatesofAmerica,2InfluenzaDivision,NationalCenterforImmunizationandRespiratoryDiseases,CentersforDiseaseControl
andPrevention,Atlanta,Georgia,UnitedStatesofAmerica, 3DepartmentsofPathologyandMicrobiology, UniversityofHongKong,PokFuLam,HongKongSpecial
AdministrativeRegion,People’sRepublicofChina
Abstract
Background: The recent emergence of a novel pandemic influenza A(H1N1) strain in humans exemplifies the rapid and
unpredictable nature of influenza virus evolution and the need for effective therapeutics and vaccines to control such
outbreaks. However, resistance to antivirals can be a formidable problem as evidenced by the currently widespread
oseltamivir- and adamantane-resistant seasonal influenza A viruses (IFV). Additional antiviral approaches with novel
mechanismsofactionareneededtocombatnovelandresistantinfluenzastrains.DAS181(FludaseTM)isasialidasefusion
proteininearlyclinicaldevelopmentwithinvitroandinvivopreclinicalactivityagainstavarietyofseasonalinfluenzastrains
andhighlypathogenicavianinfluenzastrains(A/H5N1).Here,weuseinvitro,exvivo,andinvivomodelstoevaluatethe
activityofDAS181againstseveralpandemicinfluenzaA(H1N1)viruses.
MethodsandFindings:TheactivityofDAS181againstseveralpandemicinfluenzaA(H1N1)virusisolateswasexaminedin
MDCK cells, differentiated primary human respiratory tract culture, ex-vivo human bronchi tissue and mice. DAS181
efficiently inhibited viral replication in each of these models and against all tested pandemic influenza A(H1N1) strains.
DAS181 treatment also protected mice from pandemic influenza A(H1N1)-induced pathogenesis. Furthermore, DAS181
antiviralac
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