IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6268.html
   My bibliography  Save this article

Structure-guided discovery of potent and dual-acting human parainfluenza virus haemagglutinin–neuraminidase inhibitors

Author

Listed:
  • Patrice Guillon

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

  • Larissa Dirr

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

  • Ibrahim M. El-Deeb

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

  • Moritz Winger

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

  • Benjamin Bailly

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

  • Thomas Haselhorst

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

  • Jeffrey C. Dyason

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

  • Mark von Itzstein

    (Institute for Glycomics, Gold Coast Campus, Griffith University)

Abstract

Human parainfluenza viruses (hPIVs) cause upper and lower respiratory tract disease in children that results in a significant number of hospitalizations and impacts health systems worldwide. To date, neither antiviral drugs nor vaccines are approved for clinical use against parainfluenza virus, which reinforces the urgent need for new therapeutic discovery strategies. Here we use a multidisciplinary approach to develop potent inhibitors that target a structural feature within the hPIV type 3 haemagglutinin–neuraminidase (hPIV-3 HN). These dual-acting designer inhibitors represent the most potent designer compounds and efficiently block both hPIV cell entry and virion progeny release. We also define the binding mode of these inhibitors in the presence of whole-inactivated hPIV and recombinantly expressed hPIV-3 HN by Saturation Transfer Difference NMR spectroscopy. Collectively, our study provides an antiviral preclinical candidate and a new direction towards the discovery of potential anti-parainfluenza drugs.

Suggested Citation

  • Patrice Guillon & Larissa Dirr & Ibrahim M. El-Deeb & Moritz Winger & Benjamin Bailly & Thomas Haselhorst & Jeffrey C. Dyason & Mark von Itzstein, 2014. "Structure-guided discovery of potent and dual-acting human parainfluenza virus haemagglutinin–neuraminidase inhibitors," Nature Communications, Nature, vol. 5(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6268
    DOI: 10.1038/ncomms6268
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6268
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6268?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6268. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.