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The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice

Iminosugars that are competitive inhibitors of endoplasmic reticulum (ER) α-glucosidases have been demonstrated to have antiviral activity against a diverse set of viruses. A novel iminosugar, UV-4B, has recently been shown to provide protection against lethal infections with dengue and influenza A...

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Autores principales: Warfield, Kelly L., Barnard, Dale L., Enterlein, Sven G., Smee, Donald F., Khaliq, Mansoora, Sampath, Aruna, Callahan, Michael V., Ramstedt, Urban, Day, Craig W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810261/
https://www.ncbi.nlm.nih.gov/pubmed/27072420
http://dx.doi.org/10.3390/v8030071
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author Warfield, Kelly L.
Barnard, Dale L.
Enterlein, Sven G.
Smee, Donald F.
Khaliq, Mansoora
Sampath, Aruna
Callahan, Michael V.
Ramstedt, Urban
Day, Craig W.
author_facet Warfield, Kelly L.
Barnard, Dale L.
Enterlein, Sven G.
Smee, Donald F.
Khaliq, Mansoora
Sampath, Aruna
Callahan, Michael V.
Ramstedt, Urban
Day, Craig W.
author_sort Warfield, Kelly L.
collection PubMed
description Iminosugars that are competitive inhibitors of endoplasmic reticulum (ER) α-glucosidases have been demonstrated to have antiviral activity against a diverse set of viruses. A novel iminosugar, UV-4B, has recently been shown to provide protection against lethal infections with dengue and influenza A (H1N1) viruses in mice. In the current study, the breadth of activity of UV-4B against influenza was examined ex vivo and in vivo. Efficacy of UV-4B against influenza A and B viruses was shown in primary human bronchial epithelial cells, a principal target tissue for influenza. Efficacy of UV-4B against influenza A (H1N1 and H3N2 subtypes) and influenza B was demonstrated using multiple lethal mouse models with readouts including mortality and weight loss. Clinical trials are ongoing to demonstrate safety of UV-4B and future studies to evaluate antiviral activity against influenza in humans are planned.
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spelling pubmed-48102612016-04-04 The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice Warfield, Kelly L. Barnard, Dale L. Enterlein, Sven G. Smee, Donald F. Khaliq, Mansoora Sampath, Aruna Callahan, Michael V. Ramstedt, Urban Day, Craig W. Viruses Communication Iminosugars that are competitive inhibitors of endoplasmic reticulum (ER) α-glucosidases have been demonstrated to have antiviral activity against a diverse set of viruses. A novel iminosugar, UV-4B, has recently been shown to provide protection against lethal infections with dengue and influenza A (H1N1) viruses in mice. In the current study, the breadth of activity of UV-4B against influenza was examined ex vivo and in vivo. Efficacy of UV-4B against influenza A and B viruses was shown in primary human bronchial epithelial cells, a principal target tissue for influenza. Efficacy of UV-4B against influenza A (H1N1 and H3N2 subtypes) and influenza B was demonstrated using multiple lethal mouse models with readouts including mortality and weight loss. Clinical trials are ongoing to demonstrate safety of UV-4B and future studies to evaluate antiviral activity against influenza in humans are planned. MDPI 2016-03-07 /pmc/articles/PMC4810261/ /pubmed/27072420 http://dx.doi.org/10.3390/v8030071 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Warfield, Kelly L.
Barnard, Dale L.
Enterlein, Sven G.
Smee, Donald F.
Khaliq, Mansoora
Sampath, Aruna
Callahan, Michael V.
Ramstedt, Urban
Day, Craig W.
The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice
title The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice
title_full The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice
title_fullStr The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice
title_full_unstemmed The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice
title_short The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice
title_sort iminosugar uv-4 is a broad inhibitor of influenza a and b viruses ex vivo and in mice
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4810261/
https://www.ncbi.nlm.nih.gov/pubmed/27072420
http://dx.doi.org/10.3390/v8030071
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