Abstract
To identify suitable host cells permissive for virus growth but resistant to the triterpenoid compound cicloxolone sodium (CCX), 18 cell lines were studied for tolerance to treatment for 48 h with increasing drug concentrations. IC50 values and replication indices of the IC50, at 300 μm CCX and in the absence of drug, were determined. Eight cell lines proved resistant, six sensitive and four intermediate in sensitivity to CCX. Four of the resistant cell lines were then selected as appropriate hosts for investigating the antiviral effect of CCX. Infectious yield dose–response experiments were carried out with viruses from eight different families comprising enveloped and non-enveloped DNA and RNA viruses. The RNA viruses included some with genomes that were segmented or non-segmented, positive-stranded, negative-stranded or double-stranded. No consistent relationship between sensitivity to CCX and any of these characteristics was found. Three classes of response were obtained: class 1 [VSV (Indiana), Influenza A, EHV-1 and BHV-1] showed a consistent, progressive CCX dose-dependent 100→100000-fold reduction in infectious virus yield; class 2 (Bunyamwera and Germiston, Polio-1, Reovirus-3 and Adenovirus-5) exhibited initial sensitivity (10–100-fold) but increasing the dose had minimal further effect on yield, with plateau values reached between 100 and 200 μm CCX; class 3 (SFV) appeared to be unaffected by CCX treatment. Plaque reduction assays revealed that HCMV and VZV are also highly sensitive to CCX inhibition.