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Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses

•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... Full description

Journal Title: Antiviral Research June 2013, Vol.98(3), pp.432-440
Main Author: Chang, Jinhong
Other Authors: Warren, Travis K , Zhao, Xuesen , Gill, Tina , Guo, Fang , Wang, Lijuan , Comunale, Mary Ann , Du, Yanming , Alonzi, Dominic S , Yu, Wenquan , Ye, Hong , Liu, Fei , Guo, Ju-Tao , Mehta, Anand , Cuconati, Andrea , Butters, Terry D , Bavari, Sina , Xu, Xiaodong , Block, Timothy M
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0166-3542 ; E-ISSN: 1872-9096 ; DOI: 10.1016/j.antiviral.2013.03.023
Link: http://dx.doi.org/10.1016/j.antiviral.2013.03.023
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recordid: elsevier_sdoi_10_1016_j_antiviral_2013_03_023
title: Small molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses
format: Article
creator:
  • Chang, Jinhong
  • Warren, Travis K
  • Zhao, Xuesen
  • Gill, Tina
  • Guo, Fang
  • Wang, Lijuan
  • Comunale, Mary Ann
  • Du, Yanming
  • Alonzi, Dominic S
  • Yu, Wenquan
  • Ye, Hong
  • Liu, Fei
  • Guo, Ju-Tao
  • Mehta, Anand
  • Cuconati, Andrea
  • Butters, Terry D
  • Bavari, Sina
  • Xu, Xiaodong
  • Block, Timothy M
subjects:
  • Er Α-Glucosidase
  • Imino Sugar
  • Hemorrhagic Fever Virus
  • Ebola Virus
  • Marburg Virus
  • Er Α-Glucosidase
  • Imino Sugar
  • Hemorrhagic Fever Virus
  • Ebola Virus
  • Marburg Virus
  • Medicine
  • Biology
ispartof: Antiviral Research, June 2013, Vol.98(3), pp.432-440
description: •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...
language: eng
source:
identifier: ISSN: 0166-3542 ; E-ISSN: 1872-9096 ; DOI: 10.1016/j.antiviral.2013.03.023
fulltext: fulltext
issn:
  • 0166-3542
  • 01663542
  • 1872-9096
  • 18729096
url: Link


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titleSmall molecule inhibitors of ER α-glucosidases are active against multiple hemorrhagic fever viruses
creatorChang, Jinhong ; Warren, Travis K ; Zhao, Xuesen ; Gill, Tina ; Guo, Fang ; Wang, Lijuan ; Comunale, Mary Ann ; Du, Yanming ; Alonzi, Dominic S ; Yu, Wenquan ; Ye, Hong ; Liu, Fei ; Guo, Ju-Tao ; Mehta, Anand ; Cuconati, Andrea ; Butters, Terry D ; Bavari, Sina ; Xu, Xiaodong ; Block, Timothy M
ispartofAntiviral Research, June 2013, Vol.98(3), pp.432-440
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description•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...
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•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...

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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...

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doi10.1016/j.antiviral.2013.03.023
lad01Antiviral Research
date2013-06