Iminosugars in combination with interferon and ribavirin permanently eradicate noncytopathic bovine viral diarrhea virus from persistently infected cells

Antimicrob Agents Chemother. 2008 May;52(5):1820-8. doi: 10.1128/AAC.01181-07. Epub 2008 Mar 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / chemistry
  • 1-Deoxynojirimycin / pharmacology
  • Animals
  • Antiviral Agents / pharmacology
  • Cell Line
  • Diarrhea Viruses, Bovine Viral / drug effects*
  • Diarrhea Viruses, Bovine Viral / genetics
  • Dose-Response Relationship, Drug
  • Glucosamine / analogs & derivatives*
  • Glucosamine / chemistry
  • Glucosamine / pharmacology
  • Interferons / chemistry
  • Interferons / pharmacology*
  • Molecular Structure
  • RNA, Viral / genetics
  • RNA, Viral / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribavirin / chemistry
  • Ribavirin / pharmacology*
  • Time Factors


  • Antiviral Agents
  • RNA, Viral
  • deoxynojirimycine
  • 1-Deoxynojirimycin
  • Ribavirin
  • Interferons
  • Glucosamine