Mechanism of copper-mediated inactivation of herpes simplex virus

Antimicrob Agents Chemother. 1997 Apr;41(4):812-7. doi: 10.1128/AAC.41.4.812.

Abstract

The inactivation of herpes simplex virus (HSV) by copper was enhanced by the following reducing agents at the indicated relative level: ascorbic acid >> hydrogen peroxide > cysteine. Treatment of HSV-infected cells with combinations of Cu(II) and ascorbate completely inhibited virus plaque formation to below 0.006% of the infectious virus input, while it maintained 30% viability for the host mammalian cells. The logarithm of the surviving fraction of HSV mediated by 1 mg of Cu(II) per liter and 100 mg of reducing agent per liter followed a linear relationship with the reaction time, in which the kinetic rate constant for each reducing agent was -0.87 min(-1) (r = 0.93) for ascorbate, -0.10 min(-1) (r = 0.97) for hydrogen peroxide, and -0.04 min(-1) (r = 0.97) for cysteine. The protective effects of metal chelators and catalase, the lack of effect of superoxide dismutase, and the partial protection conferred by free-radical scavengers suggest that the mechanism of copper-mediated HSV inactivation is similar to that previously reported for copper-mediated DNA damage. The sensitivity exhibited by HSV to Cu(II) and reducing agents, particularly ascorbate, might be useful in the development of therapeutic antiviral agents.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cell Survival / drug effects
  • Chelating Agents / pharmacology
  • Chlorocebus aethiops
  • Copper / pharmacology*
  • Free Radical Scavengers / pharmacology
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Kinetics
  • Reducing Agents / pharmacology
  • Simplexvirus / drug effects*
  • Vero Cells
  • Viral Plaque Assay

Substances

  • Antioxidants
  • Chelating Agents
  • Free Radical Scavengers
  • Reducing Agents
  • Copper
  • Hydrogen Peroxide