Novel sialic acid derivatives lock open the 150-loop of an influenza A virus group-1 sialidase

Santosh Rudrawar, Jeffrey C. Dyason, Marie-Anne Rameix-Welti, Faith J. Rose, Philip S. Kerry, Rupert J. M. Russell, Sylvie van der Werf, Robin J. Thomson, Nadia Naffakh and Mark von Itzstein ()
Additional contact information
Santosh Rudrawar: Institute for Glycomics, Gold Coast Campus, Griffith University
Jeffrey C. Dyason: Institute for Glycomics, Gold Coast Campus, Griffith University
Marie-Anne Rameix-Welti: Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN
Faith J. Rose: Institute for Glycomics, Gold Coast Campus, Griffith University
Philip S. Kerry: Interdisciplinary Centre for Human and Avian Influenza Research, University of St Andrews
Rupert J. M. Russell: Interdisciplinary Centre for Human and Avian Influenza Research, University of St Andrews
Sylvie van der Werf: Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN
Robin J. Thomson: Institute for Glycomics, Gold Coast Campus, Griffith University
Nadia Naffakh: Institut Pasteur, Unité de Génétique Moléculaire des Virus à ARN
Mark von Itzstein: Institute for Glycomics, Gold Coast Campus, Griffith University

Nature Communications, 2010, vol. 1, issue 1, 1-7

Abstract: 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.

Date: 2010
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/ncomms1114 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:1:y:2010:i:1:d:10.1038_ncomms1114

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms1114

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().