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Highlights: [•] A cell-based IFN-β reporter assay was established for high throughput screen. [•] This assay can be applied to any virus that is able to activate IFN response in the report cells. [•] The assay allows for identification of compounds with antiviral and innate immune response modulating activity. [Copyright &y& Elsevier]

Abstract: The aminoglycoside, geneticin (G418), was recently shown to have antiviral activity against bovine viral diarrhea virus (BVDV). Since BVDV, dengue virus (DENV) and yellow fever virus (YFV) all belong to the Flaviviridae family, it seemed possible that a common step in their life cycle might be affected by this aminoglycoside. Here it is shown that geneticin prevented the cytopathic effect (CPE) resulting from DENV-2 infection of BHK cells, in a dose-dependent manner with an 50% effective concentration (EC50) value of 3±0.4μg/ml. Geneticin had no detectable effect on CPE caused by YFV in BHK cells. Geneticin also inhibited DENV-2 viral yield with an EC50 value of 2±0.1μg/ml and an EC90 value of 20±2μg/ml. With a CC50 value of 165±5μg/ml, the selectivity index of anti-DENV activity of geneticin in BHK cells was established to be 66. Furthermore, 25μg/ml of geneticin nearly completely blocked plaque formation induced by DENV-2, but not YFV. In addition, geneticin, inhibited DENV-2 viral RNA replication and viral translation. Gentamicin, kanamycin, and the guanidinylated geneticin showed no anti-DENV activity. Neomycin and paromomycin demonstrated weak antiviral activity at high concentrations. Finally, aminoglycoside-3′-phosphotransferase activity of neomycin-resistant gene abolished antiviral activity of geneticin. [Copyright &y& Elsevier]