Antiviral Effects of an Iminosugar Derivative on Flavivirus Infections

• DOI: 10.1128/jvi.76.8.3596-3604.2002
• Publication Date: 2002-07-27T09:59:40Z
• Authors: Shu-Fen Wu; Chyan-Jang Lee; Ching-Len Liao; Raymond A. Dwek; Nicole Zitzmann; Yi-Ling Lin
• Keywords: Calnexin; Iminosugar; Sindbis virus; Flavivirus

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