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dc.contributor.authorRudrawar, Santosh
dc.contributor.authorDyason, Jeffrey C
dc.contributor.authorRameix-Welti, Marie-Anne
dc.contributor.authorRose, Faith J
dc.contributor.authorKerry, Philip S
dc.contributor.authorRussell, Rupert JM
dc.contributor.authorvan der Werf, Sylvie
dc.contributor.authorThomson, Robin J
dc.contributor.authorNaffakh, Nadia
dc.contributor.authorvon Itzstein, Mark
dc.date.accessioned2017-09-15T04:45:39Z
dc.date.available2017-09-15T04:45:39Z
dc.date.issued2010
dc.date.modified2011-03-23T05:46:04Z
dc.identifier.issn2041-1723
dc.identifier.doi10.1038/ncomms1114
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.
dc.description.peerreviewedYes
dc.description.publicationstatusYes
dc.languageEnglish
dc.language.isoen_AU
dc.publisherNature Publishing Group
dc.publisher.placeUnited Kingdom
dc.relation.ispartofstudentpublicationN
dc.relation.ispartofpagefrom1
dc.relation.ispartofpageto7
dc.relation.ispartofjournalNature Communications
dc.relation.ispartofvolume1
dc.rights.retentionY
dc.subject.fieldofresearchOrganic Chemical Synthesis
dc.subject.fieldofresearchStructural Chemistry and Spectroscopy
dc.subject.fieldofresearchVirology
dc.subject.fieldofresearchcode030503
dc.subject.fieldofresearchcode030606
dc.subject.fieldofresearchcode060506
dc.titleNovel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-sa/3.0/
dc.description.versionPublished
gro.rights.copyright© The Author(s) 2010. This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License which permits unrestricted, non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
gro.date.issued2010
gro.hasfulltextFull Text
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorThomson, Robin J.
gro.griffith.authorDyason, Jeffrey C.
gro.griffith.authorRose, Faith J.
gro.griffith.authorRudrawar, Santosh


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