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Iminosugars: A host-targeted approach to combat Flaviviridae infections
N-linked glycosylation is the most common form of protein glycosylation and is required for the proper folding, trafficking, and/or receptor binding of some host and viral proteins. As viruses lack their own glycosylation machinery, they are dependent on the host's machinery for these processes...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Author(s). Published by Elsevier B.V.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405907/ https://www.ncbi.nlm.nih.gov/pubmed/32768411 http://dx.doi.org/10.1016/j.antiviral.2020.104881 |
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author | Evans DeWald, Lisa Starr, Chloe Butters, Terry Treston, Anthony Warfield, Kelly L. |
author_facet | Evans DeWald, Lisa Starr, Chloe Butters, Terry Treston, Anthony Warfield, Kelly L. |
author_sort | Evans DeWald, Lisa |
collection | PubMed |
description | N-linked glycosylation is the most common form of protein glycosylation and is required for the proper folding, trafficking, and/or receptor binding of some host and viral proteins. As viruses lack their own glycosylation machinery, they are dependent on the host's machinery for these processes. Certain iminosugars are known to interfere with the N-linked glycosylation pathway by targeting and inhibiting α-glucosidases I and II in the endoplasmic reticulum (ER). Perturbing ER α-glucosidase function can prevent these enzymes from removing terminal glucose residues on N-linked glycans, interrupting the interaction between viral glycoproteins and host chaperone proteins that is necessary for proper folding of the viral protein. Iminosugars have demonstrated broad-spectrum antiviral activity in vitro and in vivo against multiple viruses. This review discusses the broad activity of iminosugars against Flaviviridae. Iminosugars have shown favorable activity against multiple members of the Flaviviridae family in vitro and in murine models of disease, although the activity and mechanism of inhibition can be virus-specfic. While iminosugars are not currently approved for the treatment of viral infections, their potential use as future host-targeted antiviral (HTAV) therapies continues to be investigated. |
format | Online Article Text |
id | pubmed-7405907 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | The Author(s). Published by Elsevier B.V. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74059072020-08-05 Iminosugars: A host-targeted approach to combat Flaviviridae infections Evans DeWald, Lisa Starr, Chloe Butters, Terry Treston, Anthony Warfield, Kelly L. Antiviral Res Invited Review N-linked glycosylation is the most common form of protein glycosylation and is required for the proper folding, trafficking, and/or receptor binding of some host and viral proteins. As viruses lack their own glycosylation machinery, they are dependent on the host's machinery for these processes. Certain iminosugars are known to interfere with the N-linked glycosylation pathway by targeting and inhibiting α-glucosidases I and II in the endoplasmic reticulum (ER). Perturbing ER α-glucosidase function can prevent these enzymes from removing terminal glucose residues on N-linked glycans, interrupting the interaction between viral glycoproteins and host chaperone proteins that is necessary for proper folding of the viral protein. Iminosugars have demonstrated broad-spectrum antiviral activity in vitro and in vivo against multiple viruses. This review discusses the broad activity of iminosugars against Flaviviridae. Iminosugars have shown favorable activity against multiple members of the Flaviviridae family in vitro and in murine models of disease, although the activity and mechanism of inhibition can be virus-specfic. While iminosugars are not currently approved for the treatment of viral infections, their potential use as future host-targeted antiviral (HTAV) therapies continues to be investigated. The Author(s). Published by Elsevier B.V. 2020-12 2020-08-05 /pmc/articles/PMC7405907/ /pubmed/32768411 http://dx.doi.org/10.1016/j.antiviral.2020.104881 Text en © 2020 The Author(s) Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Invited Review Evans DeWald, Lisa Starr, Chloe Butters, Terry Treston, Anthony Warfield, Kelly L. Iminosugars: A host-targeted approach to combat Flaviviridae infections |
title | Iminosugars: A host-targeted approach to combat Flaviviridae infections |
title_full | Iminosugars: A host-targeted approach to combat Flaviviridae infections |
title_fullStr | Iminosugars: A host-targeted approach to combat Flaviviridae infections |
title_full_unstemmed | Iminosugars: A host-targeted approach to combat Flaviviridae infections |
title_short | Iminosugars: A host-targeted approach to combat Flaviviridae infections |
title_sort | iminosugars: a host-targeted approach to combat flaviviridae infections |
topic | Invited Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405907/ https://www.ncbi.nlm.nih.gov/pubmed/32768411 http://dx.doi.org/10.1016/j.antiviral.2020.104881 |
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