The mechanism of the antiherpetic activity of zinc sulphate.
The molecular mechanism of the effects of zinc ions against herpes simplex virus (HSV) infection was investigated. Zinc sulphate (100 microM) in the culture medium of an HSV-infected African green monkey kidney cell line did not block viral DNA synthesis and, at this concentration, only moderate cytotoxic effects were observed in uninfected cells. Nevertheless, virus yields were reduced to less than 1% of the control. Thus the long standing hypothesis that zinc might block multiplication of HSV by selective intranuclear inhibition of the viral DNA polymerase apparently has lost its validity. Inhibition of virus growth in the absence of severe cytotoxicity must therefore result from other effects of ZnSO4. Free virus is inactivated by 15 mM-ZnSO4 within a few hours of its addition. The inactivated virus is defective in the glycoprotein-dependent functions of penetration and, to some extent, adsorption. Electron micrographs show massive deposition of zinc onto virion components. In a virion, transmembrane transport of zinc ions is not expected and the established antiviral effect is therefore explained by an inhibition of virion glycoprotein function after non-specific accumulation of zinc into many virion membrane components.
Kümel
G
G
Institut für Mikrobiologie (Virusforschung), J.W. Goethe-Universität, Frankfurt am Main, Germany.
Schrader
S
S
Zentgraf
H
H
Daus
H
H
Brendel
M
M
D000327:Adsorption; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D007700:Kinetics; D008854:Microscopy, Electron; D011991:Receptors, Virus / Q000187:drug effects / Q000502:physiology; D018139:Simplexvirus / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D013431:Sulfates / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects; D015032:Zinc / Q000494:pharmacology*; D019287:Zinc Sulfate
D000998:Antiviral Agents; D011991:Receptors, Virus; D013431:Sulfates; D019287:Zinc Sulfate; D015032:Zinc