Table 1.
In vitro activity of bicyclic iminosugars against members of the Flaviviridae family. References are provided in Fig. 1 and details for each study are included in Supplemental Table 2.
| Bicyclic Iminosugars | ||||||
|---|---|---|---|---|---|---|
| Compound(s) |
Virus |
Summary of Results | ||||
| BVDV | DENV | JEV | WNV | YFV | ||
| Castanospermine (CAST) | X | X | X | X | X |
DENV (1–4) in multiple cell types: Reduced production of infective particles. IC50 = 1–85.7 μm. Resulted in altered prM glycosylation (DENV-2 in BHK-21 cells) and impaired formation of prME heterodimers (DENV-1 in Neuro 2a cells). WNV in BHK-21 cells: minimal to no inhibitory effect at up to 500 μM YFV in BHK-21 cells: 57% reduction at 50 μM JEV in PS cells: ≤10-fold reduction in virus titer BVDV in MDBK cells: IC50 = 5–367 μM; additive activity when used in combination with NB-DNJ |
| Celgosivir (BuCast) | X | X |
DENV-1 and -2 in multiple cell types: EC50 = 0.06–51 μM. Blocked transport of NS1 and E proteins from ER to Golgi and resulted in defect in NS1 glycosylation in BHK-21 cells DENV-3 and -4 in BHK-21 cells: EC50 = 0.31–0.68 μM. BVDV: Additive or synergistic activity in MDBK cells when used in combination with ribavirin or IFN-α. |
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Abbreviations: BVDV, bovine viral diarrhea virus; DENV, dengue virus; EC50, half maximal effective concentration; ER, endoplasmic reticulum; IC50, half maximal inhibitory concentration; IFN-α, interferon alpha; JEV, Japanese encephalitis virus; MDBK, Madin-Darby bovine kidney; NS1, non-structural protein 1; PS, porcine stable; prM: precursor membrane protein; prME: precursor membrane envelope protein complex; WNV, West Nile virus; YFV, yellow fever virus.