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Rapid CommunicationMinireviews

NADPH Oxidases as Novel Pharmacologic Targets against Influenza A Virus Infection

Ross Vlahos and Stavros Selemidis
Molecular Pharmacology December 2014, 86 (6) 747-759; DOI: https://doi.org/10.1124/mol.114.095216
Ross Vlahos
Respiratory Research Group, Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne (R.V.), and Oxidant and Inflammation Biology Group, Department of Pharmacology, Monash University (S.S.), Victoria, Australia
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Stavros Selemidis
Respiratory Research Group, Lung Health Research Centre, Department of Pharmacology and Therapeutics, University of Melbourne (R.V.), and Oxidant and Inflammation Biology Group, Department of Pharmacology, Monash University (S.S.), Victoria, Australia
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Abstract

Influenza A viruses represent a major global health care challenge, with imminent pandemics, emerging antiviral resistance, and long lag times for vaccine development, raising a pressing need for novel pharmacologic strategies that ideally target the pathology irrespective of the infecting strain. Reactive oxygen species (ROS) pervade all facets of cell biology with both detrimental and protective properties. Indeed, there is compelling evidence that activation of the NADPH oxidase 2 (NOX2) isoform of the NADPH oxidase family of ROS-producing enzymes promotes lung oxidative stress, inflammation, injury, and dysfunction resulting from influenza A viruses of low to high pathogenicity, as well as impeding virus clearance. By contrast, the dual oxidase isoforms produce ROS that provide vital protective antiviral effects for the host. In this review, we propose that inhibitors of NOX2 are better alternatives than broad-spectrum antioxidant approaches for treatment of influenza pathologies, for which clinical efficacy may have been limited owing to poor bioavailability and inadvertent removal of beneficial ROS. Finally, we briefly describe the current suite of NADPH oxidase inhibitors and the molecular features of the NADPH oxidase enzymes that could be exploited by drug discovery for development of more specific and novel inhibitors to prevent or treat disease caused by influenza.

Footnotes

    • Received August 4, 2014.
    • Accepted October 8, 2014.
  • This work was supported by the Australian Research Council [Grant FT120100876]; National Health and Medical Research Council of Australia [Grant APP1027112]

  • dx.doi.org/10.1124/mol.114.095216.

  • Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 86 (6)
Molecular Pharmacology
Vol. 86, Issue 6
1 Dec 2014
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Rapid CommunicationMinireviews

NADPH Oxidases and Influenza Virus Infections

Ross Vlahos and Stavros Selemidis
Molecular Pharmacology December 1, 2014, 86 (6) 747-759; DOI: https://doi.org/10.1124/mol.114.095216

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Rapid CommunicationMinireviews

NADPH Oxidases and Influenza Virus Infections

Ross Vlahos and Stavros Selemidis
Molecular Pharmacology December 1, 2014, 86 (6) 747-759; DOI: https://doi.org/10.1124/mol.114.095216
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  • Article
    • Abstract
    • Introduction
    • Molecular Description of NADPH Oxidases
    • Exploiting Novel Interfaces in the NOX2 Oxidase Enzyme Complex to Unravel NOX2-Selective Inhibitors
    • Alternative Approaches to Suppressing Nox2 Oxidase Activity
    • Conclusion
    • Authorship Contributions
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