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dc.contributor.authorRudrawar, S
dc.contributor.authorDyason, JC
dc.contributor.authorRameix-Welti, MA
dc.contributor.authorRose, FJ
dc.contributor.authorKerry, Philip Stephen
dc.contributor.authorRussell, Rupert James Martin
dc.contributor.authorvan der Werf, S
dc.contributor.authorThomson, RJ
dc.contributor.authorNaffakh, N
dc.contributor.authorvon Itzstein, M
dc.date.accessioned2012-07-17T16:01:02Z
dc.date.available2012-07-17T16:01:02Z
dc.date.issued2010-11-16
dc.identifier.citationRudrawar , S , Dyason , JC , Rameix-Welti , MA , Rose , FJ , Kerry , P S , Russell , R J M , van der Werf , S , Thomson , RJ , Naffakh , N & von Itzstein , M 2010 , ' Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase ' , Nature Communications , vol. 1 , 113 . https://doi.org/10.1038/ncomms1114en
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 5110058
dc.identifier.otherPURE UUID: e74cc4bd-1480-437f-bad0-fbebf1f26278
dc.identifier.otherScopus: 78650045655
dc.identifier.urihttps://hdl.handle.net/10023/2997
dc.descriptionThis work was supported by the Medical Research Council and the Scottish Funding Council.en
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.language.isoeng
dc.relation.ispartofNature Communicationsen
dc.rights© 2010 Macmillan Publishers Limited. This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/en
dc.subjectQR355 Virologyen
dc.subject.lccQR355en
dc.titleNovel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidaseen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1038/ncomms1114
dc.description.statusPeer revieweden


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