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 (EC(50)) value of 3+/-0.4microg/ml.
Geneticin had no detectable effect on CPE caused by YFV in BHK cells.
Geneticin also inhibited DENV-2 viral yield with an EC(50) value of 2+/-0.1microg/ml and an EC(90) value of 20+/-2microg/ml. With a CC(50) value of 165+/-5microg/ml, the selectivity index of anti-DENV activity of
geneticin in BHK cells was established to be 66. Furthermore, 25microg/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.