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 journalArticle

65 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)23-29
Number of pages7
JournalAntiviral Research
Volume93
Issue number1
DOIs
StatePublished - Jan 1 2012

Fingerprint

2-tert-butyl-6-((3-((3-tert-butyl-2-hydroxy-5-methylphenyl)methyl)-2-hydroxy-5-methylphenyl)methyl)-4-methylphenol
Ebolavirus
Antiviral Agents
Antioxidants
Lassa virus
Marburgvirus
Infection
Rift Valley fever virus
Venezuelan Equine Encephalitis Viruses
Primates
Reactive Oxygen Species
Oxidative Stress
Fever
Up-Regulation
Vaccines
Therapeutics
Genes

Keywords

  • Antioxidant
  • Broad-spectrum
  • Filoviruses
  • High-content

ASJC Scopus subject areas

  • Pharmacology
  • Virology

Cite this

Panchal, R. G., Reid, S. P., Tran, J. P., Bergeron, A. A., Wells, J., Kota, K. P., ... Bavari, S. (2012). Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. Antiviral Research, 93(1), 23-29. https://doi.org/10.1016/j.antiviral.2011.10.011

Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. / Panchal, Rekha G.; Reid, St Patrick; Tran, Julie P.; Bergeron, Alison A.; Wells, Jay; Kota, Krishna P.; Aman, Javad; Bavari, Sina.

In: Antiviral Research, Vol. 93, No. 1, 01.01.2012, p. 23-29.

Research output: Contribution to journalArticle

Panchal, RG, Reid, SP, Tran, JP, Bergeron, AA, Wells, J, Kota, KP, Aman, J & Bavari, S 2012, 'Identification of an antioxidant small-molecule with broad-spectrum antiviral activity', Antiviral Research, vol. 93, no. 1, pp. 23-29. https://doi.org/10.1016/j.antiviral.2011.10.011
Panchal, Rekha G. ; Reid, St Patrick ; Tran, Julie P. ; Bergeron, Alison A. ; Wells, Jay ; Kota, Krishna P. ; Aman, Javad ; Bavari, Sina. / Identification of an antioxidant small-molecule with broad-spectrum antiviral activity. In: Antiviral Research. 2012 ; Vol. 93, No. 1. pp. 23-29.
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