Mechanism of copper-mediated inactivation of herpes simplex virus

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.

Highly efficient antiviral and antibacterial activities of solid-state cuprous compounds

“…These results indicate that copper ions leached from Cu 2 O were not a major contributor to the antiviral activity. Sagripanti et al showed that 50% of herpes simplex viruses (HSVs) still survived after treatment with 10 ppm of Cu 2+ ions, which may support our present results [3].…”

“…Films and fabrics coated with these inorganic powders are often used as antibacterial and antiviral materials. In copper case, many studies have demonstrated the high antimicrobial activity of copper ions [3], metals and alloys [4][5][6], and oxides [7][8][9][10]. However, no systematic study has been done in solid state copper compounds discriminating their oxidation states.…”

“…It is well known that a number of inorganic materials, such as silver [2], copper [3][4][5][6][7][8][9][10], and TiO 2 photocatalysts [11,12], display biocidal properties. Films and fabrics coated with these inorganic powders are often used as antibacterial and antiviral materials.…”

Toxicity of free and various aminocarboxylic ligands sequestered copper(II) ions to Escherichia coli

“…Cu-NTA, at the same concentration creates more DNA damages and to rectify those damages, recombinant repair mechanism and SOS repair mechanism are to be operative. Parallel to our observations, earlier researchers reported genotoxic potential of Cu in different microbial systems [43,44]. Although the precise mechanism of Cuinduced genotoxicity is not yet established, intriguing observations propose that DNA damage is an important component of Cu-toxicity facilitated through Fenton like process [41,45].…”

The growth of copper oxides on glass by flame assisted chemical vapour deposition

“…Copper appears to exert its killing effect by binding to DNA causing single strand breaks and base modification. This effect is enhanced by hydrogen peroxide and free radicals are believed to be involved in the reaction [20][21][22].…”