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dc.contributor.authorRudrawar, Santoshen_US
dc.contributor.authorDyason, Jeffreyen_US
dc.contributor.authorRameix-Welti, Marie-Anneen_US
dc.contributor.authorRose, Faithen_US
dc.contributor.authorS. Kerry, Philipen_US
dc.contributor.authorJ.M. Russell, Ruperten_US
dc.contributor.authorvan der Werf, Sylvieen_US
dc.contributor.authorThomson, Robinen_US
dc.contributor.authorNaffakh, Nadiaen_US
dc.contributor.authorvon Itzstein, Marken_US
dc.date.accessioned2017-05-03T15:56:06Z
dc.date.available2017-05-03T15:56:06Z
dc.date.issued2010en_US
dc.date.modified2011-03-23T05:46:04Z
dc.identifier.issn2041-1723en_US
dc.identifier.doi10.1038/ncomms1114en_AU
dc.identifier.urihttp://hdl.handle.net/10072/37619
dc.description.abstractInfluenza virus sialidase has an essential role in the virus' life cycle. Two distinct groups of influenza A virus sialidases have been established, that differ in the flexibility of the '150-loop', providing a more open active site in the apo form of the group-1 compared to group-2 enzymes. In this study we show, through a multidisciplinary approach, that novel sialic acid-based derivatives can exploit this structural difference and selectively inhibit the activity of group-1 sialidases. We also demonstrate that group-1 sialidases from drug-resistant mutant influenza viruses are sensitive to these designed compounds. Moreover, we have determined, by protein X-ray crystallography, that these inhibitors lock open the group-1 sialidase flexible 150-loop, in agreement with our molecular modelling prediction. This is the first direct proof that compounds may be developed to selectively target the pandemic A/H1N1, avian A/H5N1 and other group-1 sialidase-containing viruses, based on an open 150-loop conformation of the enzyme.en_US
dc.description.peerreviewedYesen_US
dc.description.publicationstatusYesen_AU
dc.languageEnglishen_US
dc.language.isoen_AU
dc.publisherNature Publishing Groupen_US
dc.publisher.placeUnited Kingdomen_US
dc.relation.ispartofstudentpublicationNen_AU
dc.relation.ispartofpagefrom1en_US
dc.relation.ispartofpageto7en_US
dc.relation.ispartofjournalNature Communicationsen_US
dc.relation.ispartofvolume1en_US
dc.rights.retentionYen_AU
dc.subject.fieldofresearchOrganic Chemical Synthesisen_US
dc.subject.fieldofresearchStructural Chemistry and Spectroscopyen_US
dc.subject.fieldofresearchVirologyen_US
dc.subject.fieldofresearchcode030503en_US
dc.subject.fieldofresearchcode030606en_US
dc.subject.fieldofresearchcode060506en_US
dc.titleNovel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidaseen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.date.issued2010
gro.hasfulltextNo Full Text


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