Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents

Ebola virus and Marburg virus are members of the family of Filoviridae and are etiological agents of a deadly hemorrhagic fever disease. The clinical symptoms of Ebola and Marburg hemorrhagic fevers are difficult to distinguish and there are currently no specific antiviral therapies against either o...

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Main Authors: Jinhong Chang, Ju-Tao Guo, Yanming Du, Timothy Block
Format: Article
Language:English
Published: Taylor & Francis Group 2013-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1038/emi.2013.77
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author Jinhong Chang
Ju-Tao Guo
Yanming Du
Timothy Block
author_facet Jinhong Chang
Ju-Tao Guo
Yanming Du
Timothy Block
author_sort Jinhong Chang
collection DOAJ
description Ebola virus and Marburg virus are members of the family of Filoviridae and are etiological agents of a deadly hemorrhagic fever disease. The clinical symptoms of Ebola and Marburg hemorrhagic fevers are difficult to distinguish and there are currently no specific antiviral therapies against either of the viruses. Therefore, a drug that is safe and effective against both would be an enormous breakthrough. We and others have shown that the folding of the glycoproteins of many enveloped viruses, including the filoviruses, is far more dependent upon the calnexin pathway of protein folding than are most host glycoproteins. Drugs that inhibit this pathway would be expected to be selectively antiviral. Indeed, as we summarize in this review, imino sugars that are competitive inhibitors of the host endoplasmic reticular α-glucosidases I and II, which are enzymes that process N-glycan on nascent glycoproteins and thereby inhibit calnexin binding to the nascent glycoproteins, have been shown to have antiviral activity against a number of enveloped viruses including filoviruses. In this review, we describe the state of development of imino sugars for use against the filoviruses, and provide an explanation for the basis of their antiviral activity as well as limitations.
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spelling doaj-art-078bed73ea0e4dbd8d4e070002904bdb2025-08-20T03:12:42ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512013-01-01211710.1038/emi.2013.77Imino sugar glucosidase inhibitors as broadly active anti-filovirus agentsJinhong Chang0Ju-Tao Guo1Yanming Du2Timothy Block3The Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USAThe Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USAThe Institute of Hepatitis and Virus Research, Doylestown, PA 18902, USAThe Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA 18902, USAEbola virus and Marburg virus are members of the family of Filoviridae and are etiological agents of a deadly hemorrhagic fever disease. The clinical symptoms of Ebola and Marburg hemorrhagic fevers are difficult to distinguish and there are currently no specific antiviral therapies against either of the viruses. Therefore, a drug that is safe and effective against both would be an enormous breakthrough. We and others have shown that the folding of the glycoproteins of many enveloped viruses, including the filoviruses, is far more dependent upon the calnexin pathway of protein folding than are most host glycoproteins. Drugs that inhibit this pathway would be expected to be selectively antiviral. Indeed, as we summarize in this review, imino sugars that are competitive inhibitors of the host endoplasmic reticular α-glucosidases I and II, which are enzymes that process N-glycan on nascent glycoproteins and thereby inhibit calnexin binding to the nascent glycoproteins, have been shown to have antiviral activity against a number of enveloped viruses including filoviruses. In this review, we describe the state of development of imino sugars for use against the filoviruses, and provide an explanation for the basis of their antiviral activity as well as limitations.https://www.tandfonline.com/doi/10.1038/emi.2013.77antiviralsEbolafilovirusglucosidase inhibitorsimino sugarsMarburg
spellingShingle Jinhong Chang
Ju-Tao Guo
Yanming Du
Timothy Block
Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents
Emerging Microbes and Infections
antivirals
Ebola
filovirus
glucosidase inhibitors
imino sugars
Marburg
title Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents
title_full Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents
title_fullStr Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents
title_full_unstemmed Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents
title_short Imino sugar glucosidase inhibitors as broadly active anti-filovirus agents
title_sort imino sugar glucosidase inhibitors as broadly active anti filovirus agents
topic antivirals
Ebola
filovirus
glucosidase inhibitors
imino sugars
Marburg
url https://www.tandfonline.com/doi/10.1038/emi.2013.77
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AT jutaoguo iminosugarglucosidaseinhibitorsasbroadlyactiveantifilovirusagents
AT yanmingdu iminosugarglucosidaseinhibitorsasbroadlyactiveantifilovirusagents
AT timothyblock iminosugarglucosidaseinhibitorsasbroadlyactiveantifilovirusagents