Affiliation:
1. MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5RJ
Abstract
At the recommended clinical dose for direct application to infected wounds tetrachloro decaoxide (TCDO) (1.0 × concentration TCDO) alone or in combination with haemoglobin proved to be cytotoxic for BHK and Flow 2002 cells, but at ≤0.1 TCDO/haem concentration BHK-21 cells tolerated treatment with the drug for 24 h retaining ≥80% cell viability. The in vitro cytotoxic effect is only partially reversible; but this could not explain the strong antiviral effect of TCDO/haem against herpes simplex virus type 1 (HSV-1) growing in BHK cells. The antiviral effect produces both a reduction in the number of virus particles assembled, and a lowering of their relative infectivity (i.e. reduced virus quality). The antiviral effect was active throughout the HSV-1 replication cycle. The quality of the viral DNA that was packaged into particles was unimpaired but unpackaged DNA was less infectious than controls. The reduction in particle numbers appeared to be due to both lowered protein synthesis and reduced virus particle assembly. TCDO/haem exhibits potent virucidal activity against HSV-1; HSV-2; Semliki Forest virus; Germiston virus; Reovirus type 3; Influenza virus type A; Feline leukaemia virus; Adenovirus type 5 and Polio virus type 1. Enveloped viruses, though varying over a wide sensitivity range were more sensitive than non-enveloped viruses. The magnitude of the virucidal effect against HSV-1 in suspension could be reduced by addition of BSA. The HSV-1 virucidal effect stems mainly from an effect of the drug on virion polypeptides. We propose that the effects of TCDO/haem result from the nonspecific chemical oxidation of susceptible chemical linkages both within and between individual proteins located intracellularly (antiviral and cytotoxic effects) or on the surface of virions (virucidal effect).