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: asco rbic acid much greater than hydrogen peroxide > cysteine. Treatment of HSV-infected cells with combinations of Cu(II) and ascorbate complete ly 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,vith the reaction time, in which the kinetic rate constant for each reducing agent was -0.87 min(-1) (r = 0.93) for asc orbate, -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 par tial protection conferred by free-radical scavengers suggest that the mechanism of copper-mediated HSV inactivation is similar to that previ ously reported for copper-mediated DNA damage, The sensitivity exhibit ed by HSV to Cu(II) and reducing agents, particularly ascorbate, might be useful in the development of therapeutic antiviral agents.