Cargando…

Iminosugar antivirals: the therapeutic sweet spot

Many viruses require the host endoplasmic reticulum protein-folding machinery in order to correctly fold one or more of their glycoproteins. Iminosugars with glucose stereochemistry target the glucosidases which are key for entry into the glycoprotein folding cycle. Viral glycoproteins are thus prev...

Descripción completa

Detalles Bibliográficos
Autores principales: Alonzi, Dominic S., Scott, Kathryn A., Dwek, Raymond A., Zitzmann, Nicole
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390498/
https://www.ncbi.nlm.nih.gov/pubmed/28408497
http://dx.doi.org/10.1042/BST20160182
_version_ 1782521473031733248
author Alonzi, Dominic S.
Scott, Kathryn A.
Dwek, Raymond A.
Zitzmann, Nicole
author_facet Alonzi, Dominic S.
Scott, Kathryn A.
Dwek, Raymond A.
Zitzmann, Nicole
author_sort Alonzi, Dominic S.
collection PubMed
description Many viruses require the host endoplasmic reticulum protein-folding machinery in order to correctly fold one or more of their glycoproteins. Iminosugars with glucose stereochemistry target the glucosidases which are key for entry into the glycoprotein folding cycle. Viral glycoproteins are thus prevented from interacting with the protein-folding machinery leading to misfolding and an antiviral effect against a wide range of different viral families. As iminosugars target host enzymes, they should be refractory to mutations in the virus. Iminosugars therefore have great potential for development as broad-spectrum antiviral therapeutics. We outline the mechanism giving rise to the antiviral activity of iminosugars, the current progress in the development of iminosugar antivirals and future prospects for this field.
format Online
Article
Text
id pubmed-5390498
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Portland Press Ltd.
record_format MEDLINE/PubMed
spelling pubmed-53904982017-05-01 Iminosugar antivirals: the therapeutic sweet spot Alonzi, Dominic S. Scott, Kathryn A. Dwek, Raymond A. Zitzmann, Nicole Biochem Soc Trans Review Articles Many viruses require the host endoplasmic reticulum protein-folding machinery in order to correctly fold one or more of their glycoproteins. Iminosugars with glucose stereochemistry target the glucosidases which are key for entry into the glycoprotein folding cycle. Viral glycoproteins are thus prevented from interacting with the protein-folding machinery leading to misfolding and an antiviral effect against a wide range of different viral families. As iminosugars target host enzymes, they should be refractory to mutations in the virus. Iminosugars therefore have great potential for development as broad-spectrum antiviral therapeutics. We outline the mechanism giving rise to the antiviral activity of iminosugars, the current progress in the development of iminosugar antivirals and future prospects for this field. Portland Press Ltd. 2017-04-15 2017-04-13 /pmc/articles/PMC5390498/ /pubmed/28408497 http://dx.doi.org/10.1042/BST20160182 Text en © 2017 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (https://creativecommons.org/licenses/by/4.0) .
spellingShingle Review Articles
Alonzi, Dominic S.
Scott, Kathryn A.
Dwek, Raymond A.
Zitzmann, Nicole
Iminosugar antivirals: the therapeutic sweet spot
title Iminosugar antivirals: the therapeutic sweet spot
title_full Iminosugar antivirals: the therapeutic sweet spot
title_fullStr Iminosugar antivirals: the therapeutic sweet spot
title_full_unstemmed Iminosugar antivirals: the therapeutic sweet spot
title_short Iminosugar antivirals: the therapeutic sweet spot
title_sort iminosugar antivirals: the therapeutic sweet spot
topic Review Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390498/
https://www.ncbi.nlm.nih.gov/pubmed/28408497
http://dx.doi.org/10.1042/BST20160182
work_keys_str_mv AT alonzidominics iminosugarantiviralsthetherapeuticsweetspot
AT scottkathryna iminosugarantiviralsthetherapeuticsweetspot
AT dwekraymonda iminosugarantiviralsthetherapeuticsweetspot
AT zitzmannnicole iminosugarantiviralsthetherapeuticsweetspot