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

doi:10.1016/j.antiviral.2009.02.204

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

Pediatrics

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

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 language	English (US)
Pages (from-to)	21-27
Number of pages	7
Journal	Antiviral research
Volume	83
Issue number	1
DOIs	https://doi.org/10.1016/j.antiviral.2009.02.204
State	Published - Jul 2009

Keywords

Aminoglycosides
Antiviral
Dengue
Flaviviruses
Geneticin

ASJC Scopus subject areas

Pharmacology
Virology

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10.1016/j.antiviral.2009.02.204

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@article{3ab3f943eca8482eb7eafffd3b0c782c,

title = "Antiviral activity of geneticin against dengue virus",

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.",

keywords = "Aminoglycosides, Antiviral, Dengue, Flaviviruses, Geneticin",

author = "Zhang, {Xianchao G.} and Mason, {Peter W.} and Dubovi, {Edward J.} and Xiaodong Xu and Nigel Bourne and Renshaw, {Randall W.} and Block, {Timothy M.} and Birk, {Alexander V.}",

note = "Funding Information: This work was supported by NIH/NIDA grant K01 DAO18262 and NIH 5U01AI061441.",

year = "2009",

month = jul,

doi = "10.1016/j.antiviral.2009.02.204",

language = "English (US)",

volume = "83",

pages = "21--27",

journal = "Antiviral research",

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T1 - Antiviral activity of geneticin against dengue virus

AU - Zhang, Xianchao G.

AU - Mason, Peter W.

AU - Dubovi, Edward J.

AU - Xu, Xiaodong

AU - Bourne, Nigel

AU - Renshaw, Randall W.

AU - Block, Timothy M.

AU - Birk, Alexander V.

N1 - Funding Information: This work was supported by NIH/NIDA grant K01 DAO18262 and NIH 5U01AI061441.

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

KW - Aminoglycosides

KW - Antiviral

KW - Dengue

KW - Flaviviruses

KW - Geneticin

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ER -

Antiviral activity of geneticin against dengue virus

Abstract

Keywords

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