Journal article
Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses
Antiviral research, Vol.98(3), pp.432-440
Jun 2013
PMCID: PMC3663898
PMID: 23578725
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
•Three imino sugars (IHVR11029, 17028 and 19029), were identified through SAR study of 120 derivatives.•These three imino sugars demonstrated broad antiviral activities against HFVs in vitro, and in vivo.•All three compounds inhibited ER α-glucosidases in vitro and in vivo.
Host cellular endoplasmic reticulum α-glucosidases I and II are essential for the maturation of viral glycosylated envelope proteins that use the calnexin mediated folding pathway. Inhibition of these glycan processing enzymes leads to the misfolding and degradation of these viral glycoproteins and subsequent reduction in virion secretion. We previously reported that, CM-10-18, an imino sugar α-glucosidase inhibitor, efficiently protected the lethality of dengue virus infection of mice. In the current study, through an extensive structure–activity relationship study, we have identified three CM-10-18 derivatives that demonstrated superior in vitro antiviral activity against representative viruses from four viral families causing hemorrhagic fever. Moreover, the three novel imino sugars significantly reduced the mortality of two of the most pathogenic hemorrhagic fever viruses, Marburg virus and Ebola virus, in mice. Our study thus proves the concept that imino sugars are promising drug candidates for the management of viral hemorrhagic fever caused by variety of viruses.
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Details
- Title
- Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses
- Creators
- Jinhong Chang - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesTravis K Warren - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesXuesen Zhao - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesTina Gill - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesFang Guo - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesLijuan Wang - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesMary Ann Comunale - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesYanming Du - Institute for Hepatitis and Virus Research, Doylestown, PA, United StatesDominic S Alonzi - Glycobiology Institute, University of Oxford, Oxford, UKWenquan Yu - Institute for Hepatitis and Virus Research, Doylestown, PA, United StatesHong Ye - Institute for Hepatitis and Virus Research, Doylestown, PA, United StatesFei Liu - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesJu-Tao Guo - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesAnand Mehta - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United StatesAndrea Cuconati - Institute for Hepatitis and Virus Research, Doylestown, PA, United StatesTerry D Butters - Glycobiology Institute, University of Oxford, Oxford, UKSina Bavari - U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD, United StatesXiaodong Xu - Institute for Hepatitis and Virus Research, Doylestown, PA, United StatesTimothy M Block - Drexel Institute for Biotechnology and Virology Research, Department of Microbiology and Immunology, Drexel University College of Medicine, Doylestown, PA, United States
- Publication Details
- Antiviral research, Vol.98(3), pp.432-440
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991014877982404721
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- Pharmacology & Pharmacy
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