Mechanism of copper-mediated inactivation of herpes simplex virus.
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.
Sagripanti
J L
JL
Center for Devices and Radiological Health, Food and Drug Administration, Rockville, Maryland 20857, USA.
Routson
L B
LB
Bonifacino
A C
AC
Lytle
C D
CD
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D003300:Copper / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007700:Kinetics; D019163:Reducing Agents / Q000494:pharmacology; D018139:Simplexvirus / Q000187:drug effects*; D014709:Vero Cells; D010948:Viral Plaque Assay
D000975:Antioxidants; D002614:Chelating Agents; D016166:Free Radical Scavengers; D019163:Reducing Agents; D003300:Copper; D006861:Hydrogen Peroxide