Iminosugars Inhibit Dengue Virus Production via Inhibition of ER Alpha-Glucosidases—Not Glycolipid Processing Enzymes
Fig 6
Celgosivir reduces circulating virus in vivo immediately prior to normal time of death in untreated controls.
Iminosugar was given orally t.i.d. (celgosivir: 33.3 mg/kg/dose) in a lethal mouse model of antibody-enhanced DENV infection. Serum samples from terminal bleeds were collected from all mice 8 hours prior to normal time of death in infected, untreated controls. (a) Circulating viral load was significantly reduced by celgosivir treatment as assayed by qRT-PCR. Statistically significant differences (*, α<0.05) were assessed by non-parametric Mann-Whitney test with Bonferroni correction for multiple comparisons of RNA (see S1 Fig). Individual readings are plotted (triangles), with the median value for each treatment indicated by the horizontal line. (b) Infectious virus level in the same serum samples was assayed by BHK-21 plaque assay. Celgosivir reduced the average viral titer, but the differences were not statistically significant by ANOVA. Data are presented as mean ± SD. Three mice were tested for each compound, and both assays were conducted in technical duplicate.