PMID- 23582447
OWN - NLM
STAT- MEDLINE
DCOM- 20140219
LR  - 20141120
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 21
IP  - 16
DP  - 2013 Aug 15
TI  - Novel imino sugar alpha-glucosidase inhibitors as antiviral compounds.
PG  - 4831-8
LID - S0968-0896(13)00227-7 [pii]
LID - 10.1016/j.bmc.2013.03.014 [doi]
AB  - Deoxynojirimycin (DNJ) based imino sugars display antiviral activity in the 
      tissue culture surrogate model of Hepatitis C (HCV), bovine viral diarrhoea virus 
      (BVDV), mediated by inhibition of ER alpha-glucosidases. Here, the antiviral 
      activities of neoglycoconjugates derived from deoxynojirimycin, and a novel 
      compound derived from deoxygalactonojirimycin, by click chemistry with 
      functionalised adamantanes are presented. Their antiviral potency, in terms of 
      both viral infectivity and virion secretion, with respect to their effect on 
      alpha-glucosidase inhibition, are reported. The distinct correlation between the 
      ability of long alkyl chain derivatives to inhibit ER alpha-glucosidases and their 
      anti-viral effect is demonstrated. Increasing alkyl linker length between DNJ and 
      triazole groups increases alpha-glucosidase inhibition and reduces the production of 
      viral progeny RNA and the maturation of the envelope polypeptide. Disruption to 
      viral glycoprotein processing, with increased glucosylation on BVDV E2 species, 
      is representative of alpha-glucosidase inhibition, whilst derivatives with longer 
      alkyl linkers also show a further decrease in infectivity of secreted virions, an 
      effect proposed to be distinct from alpha-glucosidase inhibition.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Howe, J D
AU  - Howe JD
AD  - Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, 
      South Parks Road, Oxford OX1 3QU, UK.
FAU - Smith, N
AU  - Smith N
FAU - Lee, M J-R
AU  - Lee MJ
FAU - Ardes-Guisot, N
AU  - Ardes-Guisot N
FAU - Vauzeilles, B
AU  - Vauzeilles B
FAU - Desire, J
AU  - Desire J
FAU - Baron, A
AU  - Baron A
FAU - Bleriot, Y
AU  - Bleriot Y
FAU - Sollogoub, M
AU  - Sollogoub M
FAU - Alonzi, D S
AU  - Alonzi DS
FAU - Butters, T D
AU  - Butters TD
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130322
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Antiviral Agents)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Glycoside Hydrolase Inhibitors)
RN  - 0 (Imino Sugars)
RN  - 0 (Viral Envelope Proteins)
RN  - 0 (deoxynojirimycine)
RN  - 0 (gp53, bovine viral diarrhea virus)
RN  - 19130-96-2 (1-Deoxynojirimycin)
RN  - EC 3.2.1.20 (alpha-Glucosidases)
RN  - N08U5BOQ1K (Glucosamine)
SB  - IM
MH  - 1-Deoxynojirimycin/chemistry
MH  - Animals
MH  - Antiviral Agents/chemical synthesis/*chemistry/pharmacology
MH  - Cattle
MH  - Cell Survival/drug effects
MH  - Click Chemistry
MH  - Diarrhea Viruses, Bovine Viral/metabolism
MH  - Dogs
MH  - Enzyme Inhibitors/chemical synthesis/*chemistry/pharmacology
MH  - Glucosamine/analogs & derivatives/chemistry
MH  - *Glycoside Hydrolase Inhibitors
MH  - Glycosylation
MH  - Hepacivirus/metabolism
MH  - Imino Sugars/chemical synthesis/*chemistry/pharmacology
MH  - Madin Darby Canine Kidney Cells
MH  - Viral Envelope Proteins/metabolism
MH  - Virus Replication/drug effects
MH  - alpha-Glucosidases/metabolism
OTO - NOTNLM
OT  - Bovine viral diarrhea virus
OT  - Endoplasmic reticulum
OT  - Glucosidases
OT  - Imino sugars
OT  - Neoglycoconjugates
EDAT- 2013/04/16 06:00
MHDA- 2014/02/20 06:00
CRDT- 2013/04/16 06:00
PHST- 2012/11/06 00:00 [received]
PHST- 2013/03/13 00:00 [revised]
PHST- 2013/03/14 00:00 [accepted]
PHST- 2013/04/16 06:00 [entrez]
PHST- 2013/04/16 06:00 [pubmed]
PHST- 2014/02/20 06:00 [medline]
AID - S0968-0896(13)00227-7 [pii]
AID - 10.1016/j.bmc.2013.03.014 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2013 Aug 15;21(16):4831-8. doi: 10.1016/j.bmc.2013.03.014. Epub 
      2013 Mar 22.