Identification of an antioxidant small-molecule with broad-spectrum antiviral activity

Rekha G. Panchal; St Patrick Reid; Julie P. Tran; Alison A. Bergeron; Jay Wells; Krishna P. Kota; Javad Aman; Sina Bavari

doi:10.1016/j.antiviral.2011.10.011

Identification of an antioxidant small-molecule with broad-spectrum antiviral activity

Rekha G. Panchal, St Patrick Reid, Julie P. Tran, Alison A. Bergeron, Jay Wells, Krishna P. Kota, Javad Aman, Sina Bavari

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

77 Scopus citations

Abstract

The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets.

Original language	English (US)
Pages (from-to)	23-29
Number of pages	7
Journal	Antiviral Research
Volume	93
Issue number	1
DOIs	https://doi.org/10.1016/j.antiviral.2011.10.011
State	Published - Jan 2012
Externally published	Yes

Keywords

Antioxidant
Broad-spectrum
Filoviruses
High-content

ASJC Scopus subject areas

Pharmacology
Virology

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10.1016/j.antiviral.2011.10.011

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title = "Identification of an antioxidant small-molecule with broad-spectrum antiviral activity",

abstract = "The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets.",

keywords = "Antioxidant, Broad-spectrum, Filoviruses, High-content",

author = "Panchal, {Rekha G.} and Reid, {St Patrick} and Tran, {Julie P.} and Bergeron, {Alison A.} and Jay Wells and Kota, {Krishna P.} and Javad Aman and Sina Bavari",

note = "Funding Information: We thank Xiaoli Chi , Julie Constantino and Cary Retterer for technical support, Dr. Robert (Dutch) Boltz for high-content imaging and image analysis. This project has been funded by Defense Threat Reduction Agency (to R.G. Panchal and S. Bavari). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the US Army . ",

year = "2012",

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doi = "10.1016/j.antiviral.2011.10.011",

language = "English (US)",

volume = "93",

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AU - Panchal, Rekha G.

AU - Reid, St Patrick

AU - Tran, Julie P.

AU - Bergeron, Alison A.

AU - Wells, Jay

AU - Kota, Krishna P.

AU - Aman, Javad

AU - Bavari, Sina

N1 - Funding Information: We thank Xiaoli Chi , Julie Constantino and Cary Retterer for technical support, Dr. Robert (Dutch) Boltz for high-content imaging and image analysis. This project has been funded by Defense Threat Reduction Agency (to R.G. Panchal and S. Bavari). Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the US Army .

PY - 2012/1

Y1 - 2012/1

N2 - The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets.

AB - The highly lethal filoviruses, Ebola and Marburg cause severe hemorrhagic fever in humans and non-human primates. To date there are no licensed vaccines or therapeutics to counter these infections. Identifying novel pathways and host targets that play an essential role during infection will provide potential targets to develop therapeutics. Small molecule chemical screening for Ebola virus inhibitors resulted in identification of a compound NSC 62914. The compound was found to exhibit anti-filovirus activity in cell-based assays and in vivo protected mice following challenge with Ebola or Marburg viruses. Additionally, the compound was found to inhibit Rift Valley fever virus, Lassa virus and Venezuelan equine encephalitis virus in cell-based assays. Investigation of the mechanism of action of the compound revealed that it had antioxidant properties. Specifically, compound NSC 62914 was found to act as a scavenger of reactive oxygen species, and to up-regulate oxidative stress-induced genes. However, four known antioxidant compounds failed to inhibit filovirus infection, thus suggesting that the mechanistic basis of the antiviral function of the antioxidant NSC 62914 may involve modulation of multiple signaling pathways/targets.

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Identification of an antioxidant small-molecule with broad-spectrum antiviral activity

Abstract

Keywords

ASJC Scopus subject areas

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