Antiviral activity of geneticin against dengue virus

Xianchao G. Zhang, Peter W. Mason, Edward J. Dubovi, Xiaodong Xu, Nigel Bourne, Randall W. Renshaw, Timothy M. Block, Alexander V. Birk

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 ± 0.4 μg/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 ± 0.1 μg/ml and an EC90 value of 20 ± 2 μg/ml. With a CC50 value of 165 ± 5 μg/ml, the selectivity index of anti-DENV activity of geneticin in BHK cells was established to be 66. Furthermore, 25 μg/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.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalAntiviral Research
Volume83
Issue number1
DOIs
StatePublished - Jul 2009

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Dengue Virus
Antiviral Agents
Yellow fever virus
Bovine Viral Diarrhea Viruses
Neomycin
Aminoglycosides
Flaviviridae
antibiotic G 418
Paromomycin
Kanamycin Kinase
Kanamycin
Dengue
Viral RNA
Virus Diseases
Gentamicins
Life Cycle Stages

Keywords

  • Aminoglycosides
  • Antiviral
  • Dengue
  • Flaviviruses
  • Geneticin

ASJC Scopus subject areas

  • Virology
  • Pharmacology

Cite this

Zhang, X. G., Mason, P. W., Dubovi, E. J., Xu, X., Bourne, N., Renshaw, R. W., ... Birk, A. V. (2009). Antiviral activity of geneticin against dengue virus. Antiviral Research, 83(1), 21-27. https://doi.org/10.1016/j.antiviral.2009.02.204

Antiviral activity of geneticin against dengue virus. / Zhang, Xianchao G.; Mason, Peter W.; Dubovi, Edward J.; Xu, Xiaodong; Bourne, Nigel; Renshaw, Randall W.; Block, Timothy M.; Birk, Alexander V.

In: Antiviral Research, Vol. 83, No. 1, 07.2009, p. 21-27.

Research output: Contribution to journalArticle

Zhang, XG, Mason, PW, Dubovi, EJ, Xu, X, Bourne, N, Renshaw, RW, Block, TM & Birk, AV 2009, 'Antiviral activity of geneticin against dengue virus', Antiviral Research, vol. 83, no. 1, pp. 21-27. https://doi.org/10.1016/j.antiviral.2009.02.204
Zhang, Xianchao G. ; Mason, Peter W. ; Dubovi, Edward J. ; Xu, Xiaodong ; Bourne, Nigel ; Renshaw, Randall W. ; Block, Timothy M. ; Birk, Alexander V. / Antiviral activity of geneticin against dengue virus. In: Antiviral Research. 2009 ; Vol. 83, No. 1. pp. 21-27.
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