In vitro activity of pleconaril and AG7088 against selected serotypes and clinical isolates of human rhinoviruses.

BACKGROUND: We tested the in vitro activity of pleconaril and AG7088 against five numbered human rhinovirus (HRV) serotypes and 46 clinical HRV isolates of undefined serotype recovered from patients with common colds. Antiviral effect of pleconaril and AG7088 were assessed by cytophathic effect (CPE) inhibition assays in Ohio HeLaI cells using microscopic and spectrophotometric methods. Both compounds were tested at concentrations of 1.0, 0.1 and 0.01 microg/ml. For the numbered HRV serotypes, the median EC(50) value determined by the microscopic CPE inhibition was slightly better for AG7088 compared to pleconaril (P=0.02) but was similar by spectrophotometric assay (P=0.15). For clinical HRV isolates the median EC(50) value determined microscopically was 0.01 microg/ml range, <0.01-0.04 microg/ml) for AG7088 compared to 0.07 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). The median EC(50) value determined by spectrophotometric assay was 0.01 microg/ml (range, <0.01-0.04 microg/ml) for AG7088 compared to 0.04 microg/ml (range, <0.01->1 microg/ml) for pleconaril (P<0.001). By either the microscopic or spectrophotometric methods the median EC(50) value of AG7088 was <1.0 microg/ml for all isolates and was >10.0 microg/ml of pleconaril for approximately 9% of isolates. In vitro AG7088 appeared to be more potent and to have a broader antirhinoviral spectrum than pleconaril among clinical HRV isolates. The clinical relevance of these in vitro results needs to be determined in controlled clinical trials.