Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Evans DeWald, Lisa, Starr, Chloe, Butters, Terry, Treston, Anthony, Warfield, Kelly L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier B.V. 2020
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
_version_ 1783567341879033856
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
work_keys_str_mv AT evansdewaldlisa iminosugarsahosttargetedapproachtocombatflaviviridaeinfections
AT starrchloe iminosugarsahosttargetedapproachtocombatflaviviridaeinfections
AT buttersterry iminosugarsahosttargetedapproachtocombatflaviviridaeinfections
AT trestonanthony iminosugarsahosttargetedapproachtocombatflaviviridaeinfections
AT warfieldkellyl iminosugarsahosttargetedapproachtocombatflaviviridaeinfections