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Please use this identifier to cite or link to this item: http://hdl.handle.net/10023/2997
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Title: Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase
Authors: Rudrawar, S
Dyason, JC
Rameix-Welti, MA
Rose, FJ
Kerry, Philip Stephen
Russell, Rupert James Martin
van der Werf, S
Thomson, RJ
Naffakh, N
von Itzstein, M
Keywords: QR355 Virology
Issue Date: 16-Nov-2010
Citation: Rudrawar , S , Dyason , J C , Rameix-Welti , M A , Rose , F J , Kerry , P S , Russell , R J M , van der Werf , S , Thomson , R J , 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 .
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.
Version: Publisher PDF
Description: This work was supported by the Medical Research Council and the Scottish Funding Council.
Status: Peer reviewed
URI: http://hdl.handle.net/10023/2997
DOI: http://dx.doi.org/10.1038/ncomms1114
ISSN: 2041-1723
Type: Journal article
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/
Appears in Collections:University of St Andrews Research
Biology Research
Biomedical Sciences Research Complex (BSRC) Research



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