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  • New antiviral approaches for human parainfluenza: Inhibiting the haemagglutinin-neuraminidase

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    Author(s)
    Chibanga, Vimbaishe P
    Dirr, Larissa
    Guillon, Patrice
    El-Deeb, Ibrahim M
    Bailly, Benjamin
    Thomson, Robin J
    von Itzstein, Mark
    Griffith University Author(s)
    Chibanga, Vimbaishe P.
    Dirr, Larissa E.
    Guillon, Patrice M.
    von Itzstein, Mark
    Bailly, Benjamin
    El-Deeb, Ibrahim Mustafa
    Thomson, Robin J.
    Year published
    2019
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    Abstract
    Human parainfluenza viruses cause acute respiratory tract infections and disease predominantly in young children and immunocompromised individuals. Currently, there are no vaccines to prevent hPIV infections, nor licensed anti-hPIV drugs. There is therefore a need for specific antiviral therapies to decrease the morbidity and mortality associated with hPIV diseases. Haemagglutinin-neuraminidase (HN) is one of two hPIV surface proteins with critical roles in host receptor recognition, binding and cleavage; it has been explored as a key drug development target for the past few decades with variable success. Recent advancements ...
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    Human parainfluenza viruses cause acute respiratory tract infections and disease predominantly in young children and immunocompromised individuals. Currently, there are no vaccines to prevent hPIV infections, nor licensed anti-hPIV drugs. There is therefore a need for specific antiviral therapies to decrease the morbidity and mortality associated with hPIV diseases. Haemagglutinin-neuraminidase (HN) is one of two hPIV surface proteins with critical roles in host receptor recognition, binding and cleavage; it has been explored as a key drug development target for the past few decades with variable success. Recent advancements in computational modelling and the availability of the X-ray crystal structure of hPIV3 HN have improved our understanding of the structural and mechanistic features of HN. This review explores structural features of the HN protein that are being exploited for structure-guided inhibitor design. We describe past and present hPIV HN inhibition strategies based on sialic acid scaffolds, together with other novel approaches that decrease hPIV infectivity. Although many HN inhibitors have been developed and evaluated as anti-hPIV agents, currently only a host-directed therapy (DAS181) has succeeded in phase II clinical drug trials. Hence, the review concludes with future considerations for targeting the specific function(s) of hPIV HN and suggestions for antiviral drug design.
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    Journal Title
    Antiviral Research
    Volume
    167
    DOI
    https://doi.org/10.1016/j.antiviral.2019.04.001
    Copyright Statement
    © 2019 Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence (http://creativecommons.org/licenses/by-nc-nd/4.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.
    Subject
    Microbiology
    Medical Microbiology
    Pharmacology and Pharmaceutical Sciences
    Publication URI
    http://hdl.handle.net/10072/386189
    Collection
    • Journal articles

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