Antiviral effects of an iminosugar derivative on flavivirus infections

J Virol. 2002 Apr;76(8):3596-604. doi: 10.1128/jvi.76.8.3596-3604.2002.


Endoplasmic reticulum (ER) alpha-glucosidase inhibitors, which block the trimming step of N-linked glycosylation, have been shown to eliminate the production of several ER-budding viruses. Here we investigated the effects of one such inhibitor, N-nonyl-deoxynojirimycin (NN-DNJ), a 9-carbon alkyl iminosugar derivative, on infection by Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2). In the presence of NN-DNJ, JEV and DEN-2 infections were suppressed in a dose-dependent manner. This inhibitory effect appeared to influence DEN-2 infection more than JEV infection, since lower concentrations of NN-DNJ substantially blocked DEN-2 replication. Secretion of the flaviviral glycoproteins E and NS1 was greatly reduced, and levels of DEN-2 viral RNA replication measured by fluorogenic reverse transcription-PCR were also decreased, by NN-DNJ. Notably, the viral glycoproteins, prM, E, and NS1 were found to associate transiently with the ER chaperone calnexin, and this interaction was affected by NN-DNJ, suggesting a potential role of calnexin in the folding of flaviviral glycoproteins. Additionally, in a mouse model of lethal challenge by JEV infection, oral delivery of NN-DNJ reduced the mortality rate. These findings show that NN-DNJ has an antiviral effect on flavivirus infection, likely through interference with virus replication at the posttranslational modification level, occurring mainly in the ER.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Deoxynojirimycin / analogs & derivatives*
  • 1-Deoxynojirimycin / pharmacology*
  • 1-Deoxynojirimycin / therapeutic use
  • Animals
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Cell Line
  • Cricetinae
  • Dengue / virology
  • Dengue Virus / drug effects*
  • Dengue Virus / physiology
  • Encephalitis Virus, Japanese / drug effects*
  • Encephalitis Virus, Japanese / physiology
  • Encephalitis, Japanese / drug therapy*
  • Encephalitis, Japanese / virology
  • Female
  • Glycoside Hydrolase Inhibitors
  • Mice
  • Mice, Inbred ICR


  • Antiviral Agents
  • Glycoside Hydrolase Inhibitors
  • N-nonyl-1-deoxynojirimycin
  • 1-Deoxynojirimycin