TABLE 1.
Biological profile of RSV polymerase inhibitors as compared to ribavirina
| Compound | Polymerase IC50 (μM) | Antiviral EC50 (μM) | Cytotoxicity CC50 (μM) | Selectivity (CC50/EC50) | Mouse model log titer reduction (N)b |
|---|---|---|---|---|---|
| B | 10.4 | 2.1 | 16 | 8 | ND |
| A | 4.5 | 1.3 | 7.7 | 6 | ND |
| C | 0.88 | 0.25 | 7.6 | 30 | 0.12 (6) |
| E | 0.66 | 0.10 | 10.7 | 107 | 0.38* (12) |
| D | 0.089 | 0.021 | 8.4 | 400 | 0.60* (12) |
| Ribavirin | ND | 6.9 | 200 | 29 | 0.04 (12) |
a
RSV polymerase assays were performed using the poly-A capture assay and antiviral activity was measured by ELISA. Cytotoxicity was determined using an MTT assay. Values shown are the average of at least three determinations.
b
The effect of inhibitors on RSV lung titers in mice was determined using the number of animals shown in parentheses. Vehicle-treated animals (n = 24) exhibited lung titers of 3.52 ± 0.04 log. The doses administered were as follows: compound C, 0.4 mg/kg/day; compound D, 0.4 mg/kg/day and compound E, 4.1 mg/kg/day. Ribavirin (Sigma) was administered at a dose of 10 mg/kg/day in vehicle. *, significantly different from vehicle; ND, not determined.