TABLE 2.
Characterization of lead hits in the HCV replication cycle
| Primary hita | Entryb |
Replicationb (replicon) | Single cycleb (HCVsc) | Target stagec | |
|---|---|---|---|---|---|
| HCVpp | VSV-Gpp | ||||
| Amperozide hydrochloride | 107 ± 29.9 | 105 ± 33.6 | 94.3 ± 40.9 | 11.0 ± 8.05 | Undetermined |
| BIO | 104 ± 31.9 | 115 ± 17.2 | 88.3 ± 34.8 | 55.3 ± 0.360 | Assembly/secretion |
| Cyclosporine | 47.5 ± 21.5 | 87.0 ± 14.0 | 0.750 ± 2.06 | 0.750 ± 0.310 | Replication |
| Diacylglycerol kinase inhibitor I | 80.2 ± 19.1 | 73.8 ± 19.7 | 110 ± 26.4 | 50.1 ± 8.87 | Assembly/secretion |
| Dilazep hydrochloride | 38.5 ± 15.5 | 87.9 ± 9.60 | 61.0 ± 6.12 | 2.87 ± 2.67 | Entry |
| Flunarizine dihydrochloride | 124 ± 30.4 | 88.3 ± 13.1 | 94.4 ± 14.6 | 14.9 ± 7.60 | Undetermined |
| GW2974 | 65.7 ± 32.5 | 94.0 ± 20.2 | 123 ± 54.3 | 36.5 ± 2.48 | Entry? |
| Ritanserin | 87.9 ± 23.3 | 76.4 ± 29.7 | 68.9 ± 24.0 | 56.4 ± 2.91 | Assembly/secretion |
| Roscovitine | 45.5 ± 23.3 | 82.9 ± 21.0 | 109 ± 33.7 | 27.0 ± 19.0 | Entry |
| SB 242084 dihydrochloride hydrate | 119 ± 32.5 | 79.4 ± 22.9 | 30.7 ± 21.3 | 12.4 ± 1.22 | Replication |
a
All the compounds were tested at 10 μM concentration.
b
The numbers (means ± SD) are percentages of the DMSO control from 5 replicates.
c
Determination of the specific target stage of the HCV replication cycle is based on various virologic assays (<50% of the control was considered significant).