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Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase
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dc.contributor.author | Rudrawar, S | |
dc.contributor.author | Dyason, JC | |
dc.contributor.author | Rameix-Welti, MA | |
dc.contributor.author | Rose, FJ | |
dc.contributor.author | Kerry, Philip Stephen | |
dc.contributor.author | Russell, Rupert James Martin | |
dc.contributor.author | van der Werf, S | |
dc.contributor.author | Thomson, RJ | |
dc.contributor.author | Naffakh, N | |
dc.contributor.author | von Itzstein, M | |
dc.date.accessioned | 2012-07-17T16:01:02Z | |
dc.date.available | 2012-07-17T16:01:02Z | |
dc.date.issued | 2010-11-16 | |
dc.identifier.citation | Rudrawar , 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/ncomms1114 | en |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | PURE: 5110058 | |
dc.identifier.other | PURE UUID: e74cc4bd-1480-437f-bad0-fbebf1f26278 | |
dc.identifier.other | Scopus: 78650045655 | |
dc.identifier.uri | https://hdl.handle.net/10023/2997 | |
dc.description | This work was supported by the Medical Research Council and the Scottish Funding Council. | en |
dc.description.abstract | Influenza 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.iso | eng | |
dc.relation.ispartof | Nature Communications | en |
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.subject | QR355 Virology | en |
dc.subject.lcc | QR355 | en |
dc.title | Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase | en |
dc.type | Journal article | en |
dc.description.version | Publisher PDF | en |
dc.contributor.institution | University of St Andrews. School of Biology | en |
dc.contributor.institution | University of St Andrews. Biomedical Sciences Research Complex | en |
dc.identifier.doi | https://doi.org/10.1038/ncomms1114 | |
dc.description.status | Peer reviewed | en |
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