PMID- 18316522
OWN - NLM
STAT- MEDLINE
DCOM- 20080813
LR  - 20211020
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 52
IP  - 5
DP  - 2008 May
TI  - Iminosugars in combination with interferon and ribavirin permanently eradicate 
      noncytopathic bovine viral diarrhea virus from persistently infected cells.
PG  - 1820-8
LID - 10.1128/AAC.01181-07 [doi]
AB  - We evaluated interferon (IFN) and ribavirin (RBV) as dual therapy and as part of 
      triple-combination therapies with the iminosugars N-butyl-deoxynojirimycin 
      (NB-DNJ), N-nonyl-deoxynojirimycin, and 
      N-7-oxanonyl-6-deoxymethyl-galactonojirimycin. The ability of these compounds to 
      clear bovine viral diarrhea virus (BVDV), a surrogate model for hepatitis C virus 
      (HCV), from a persistently infected Madin-Darby bovine kidney cells cell line was 
      determined by monitoring the secretion of viral RNA and the infectivity of 
      secreted virions. In the BVDV system, after treatment with IFN-RBV alone, viral 
      rebound was observed immediately after removal of the drugs. In contrast, we 
      demonstrate that a triple drug combination of IFN, RBV, and an iminosugar 
      eradicated the BVDV infection in a time- and a dose-dependent manner, leading to 
      sustained viral clearance. Importantly, in the case of NB-DNJ, the sustained 
      viral clearance was achieved by using physiologically relevant and tolerated drug 
      concentrations. Therefore, the use of a triple-combination therapy that includes 
      an iminosugar may prove to be of greater therapeutic value for the treatment of 
      HCV infection than the use of IFN-RBV alone.
FAU - Woodhouse, Stephen D
AU  - Woodhouse SD
AD  - Oxford Glycobiology Institute, Department of Biochemistry, South Parks Road, 
      Oxford OX1 3QU, United Kingdom.
FAU - Smith, Caroline
AU  - Smith C
FAU - Michelet, Maud
AU  - Michelet M
FAU - Branza-Nichita, Norica
AU  - Branza-Nichita N
FAU - Hussey, Mark
AU  - Hussey M
FAU - Dwek, Raymond A
AU  - Dwek RA
FAU - Zitzmann, Nicole
AU  - Zitzmann N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080303
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antiviral Agents)
RN  - 0 (RNA, Viral)
RN  - 0 (deoxynojirimycine)
RN  - 19130-96-2 (1-Deoxynojirimycin)
RN  - 49717AWG6K (Ribavirin)
RN  - 9008-11-1 (Interferons)
RN  - N08U5BOQ1K (Glucosamine)
SB  - IM
MH  - 1-Deoxynojirimycin/chemistry/pharmacology
MH  - Animals
MH  - Antiviral Agents/pharmacology
MH  - Cell Line
MH  - Diarrhea Viruses, Bovine Viral/*drug effects/genetics
MH  - Dose-Response Relationship, Drug
MH  - Glucosamine/*analogs & derivatives/chemistry/pharmacology
MH  - Interferons/chemistry/*pharmacology
MH  - Molecular Structure
MH  - RNA, Viral/genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribavirin/chemistry/*pharmacology
MH  - Time Factors
PMC - PMC2346636
EDAT- 2008/03/05 09:00
MHDA- 2008/08/14 09:00
PMCR- 2008/11/01
CRDT- 2008/03/05 09:00
PHST- 2008/03/05 09:00 [pubmed]
PHST- 2008/08/14 09:00 [medline]
PHST- 2008/03/05 09:00 [entrez]
PHST- 2008/11/01 00:00 [pmc-release]
AID - AAC.01181-07 [pii]
AID - 1181-07 [pii]
AID - 10.1128/AAC.01181-07 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2008 May;52(5):1820-8. doi: 10.1128/AAC.01181-07. 
      Epub 2008 Mar 3.