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Viruses 2016, 8(3), 71; doi:10.3390/v8030071

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

1
Emergent BioSolutions, Gaithersburg, MD 20879, USA
2
Institute for Antiviral Research, Utah State University, Logan, UT 84322-5600, USA
3
Integrated Biotherapeutics Inc., Gaithersburg, MD 20878, USA
4
Division of Infectious Diseases, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA
5
Unither Virology, LLC, Silver Spring, MD 20910, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Curt Hagedorn
Received: 8 December 2015 / Revised: 11 February 2016 / Accepted: 16 February 2016 / Published: 7 March 2016
(This article belongs to the Section Antivirals & Vaccines)
View Full-Text   |   Download PDF [770 KB, uploaded 7 March 2016]   |  

Abstract

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. View Full-Text
Keywords: Iminosugar; UV-4B; influenza; human bronchial epithelial cells; antiviral; mice Iminosugar; UV-4B; influenza; human bronchial epithelial cells; antiviral; mice
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Warfield, K.L.; Barnard, D.L.; Enterlein, S.G.; Smee, D.F.; Khaliq, M.; Sampath, A.; Callahan, M.V.; Ramstedt, U.; Day, C.W. The Iminosugar UV-4 is a Broad Inhibitor of Influenza A and B Viruses ex Vivo and in Mice. Viruses 2016, 8, 71.

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