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A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)

Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such...

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Autores principales: Warfield, Kelly L., Plummer, Emily, Alonzi, Dominic S., Wolfe, Gary W., Sampath, Aruna, Nguyen, Tam, Butters, Terry D., Enterlein, Sven G., Stavale, Eric J., Shresta, Sujan, Ramstedt, Urban
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452912/
https://www.ncbi.nlm.nih.gov/pubmed/25984714
http://dx.doi.org/10.3390/v7052404
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author Warfield, Kelly L.
Plummer, Emily
Alonzi, Dominic S.
Wolfe, Gary W.
Sampath, Aruna
Nguyen, Tam
Butters, Terry D.
Enterlein, Sven G.
Stavale, Eric J.
Shresta, Sujan
Ramstedt, Urban
author_facet Warfield, Kelly L.
Plummer, Emily
Alonzi, Dominic S.
Wolfe, Gary W.
Sampath, Aruna
Nguyen, Tam
Butters, Terry D.
Enterlein, Sven G.
Stavale, Eric J.
Shresta, Sujan
Ramstedt, Urban
author_sort Warfield, Kelly L.
collection PubMed
description Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher’s disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics.
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spelling pubmed-44529122015-06-04 A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue) Warfield, Kelly L. Plummer, Emily Alonzi, Dominic S. Wolfe, Gary W. Sampath, Aruna Nguyen, Tam Butters, Terry D. Enterlein, Sven G. Stavale, Eric J. Shresta, Sujan Ramstedt, Urban Viruses Article Iminosugars are capable of targeting the life cycles of multiple viruses by blocking host endoplasmic reticulum α-glucosidase enzymes that are required for competent replication of a variety of enveloped, glycosylated viruses. Iminosugars as a class are approved for use in humans with diseases such as diabetes and Gaucher’s disease, providing evidence for safety of this class of compounds. The in vitro antiviral activity of iminosugars has been described in several publications with a subset of these demonstrating in vivo activity against flaviviruses, herpesviruses, retroviruses and filoviruses. Although there is compelling non-clinical in vivo evidence of antiviral efficacy, the efficacy of iminosugars as antivirals has yet to be demonstrated in humans. In the current study, we report a novel iminosugar, UV-12, which has efficacy against dengue and influenza in mouse models. UV-12 exhibits drug-like properties including oral bioavailability and good safety profile in mice and guinea pigs. UV-12 is an example of an iminosugar with activity against multiple virus families that should be investigated in further safety and efficacy studies and demonstrates potential value of this drug class as antiviral therapeutics. MDPI 2015-05-13 /pmc/articles/PMC4452912/ /pubmed/25984714 http://dx.doi.org/10.3390/v7052404 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Warfield, Kelly L.
Plummer, Emily
Alonzi, Dominic S.
Wolfe, Gary W.
Sampath, Aruna
Nguyen, Tam
Butters, Terry D.
Enterlein, Sven G.
Stavale, Eric J.
Shresta, Sujan
Ramstedt, Urban
A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)
title A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)
title_full A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)
title_fullStr A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)
title_full_unstemmed A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)
title_short A Novel Iminosugar UV-12 with Activity against the Diverse Viruses Influenza and Dengue (Novel Iminosugar Antiviral for Influenza and Dengue)
title_sort novel iminosugar uv-12 with activity against the diverse viruses influenza and dengue (novel iminosugar antiviral for influenza and dengue)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452912/
https://www.ncbi.nlm.nih.gov/pubmed/25984714
http://dx.doi.org/10.3390/v7052404
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