TABLE 2.
In vitro antiviral activity of HCV inhibitors against intergenotypic chimeric repliconsa
| Replicon construct | RLuc count (103) | Macrocyclic protease inhibitor
|
IFN-α
|
Nucleoside active site
|
Benz-imidazole NNI1
|
Thiophene carboxylic acid NNI2
|
Benzothiadiazine NNI3
|
Benzofuran NNI4
|
|||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EC50 (μM) | FC | EC50 (IU/ml) | FC | EC50 (μM) | FC | EC50 (μM) | FC | EC50 (μM) | FC | EC50 (μM) | FC | EC50 (μM) | FC | ||
| GT1b, Con-1 | 490 | 0.0066 | 1.3 | 0.91 | 0.90 | 0.025 | 0.033 | 0.042 | |||||||
| GT1a, H77 | 450 | 0.020 | 3 | 1.1 | 1 | 0.53 | 1 | 0.49 | 1 | 0.02 | 1 | 0.14 | 4 | 0.038 | 1 |
| GT2a, JFH1 | 318 | 0.74 | 112 | 1 | 1 | 3.6 | 4 | 6.9 | 8 | 6.1 | 244 | >32 | >970 | 0.13 | 3 |
| GT2bNS5B, Con-1 | 370 | 0.026 | 4 | 0.48 | 0.4 | 1.3 | 1 | 30 | 33 | >32 | >1,280 | >32 | >970 | 0.055 | 1 |
| GT3aNS5B, Con-1 | 120 | 0.022 | 3 | 0.23 | 0.2 | 2.9 | 3.2 | 0.21 | 0.2 | >32 | >1,280 | >32 | >970 | 0.051 | 1 |
| GT4aNS5B, Con-1 | 500 | 0.053 | 8 | 2.5 | 2 | 1.4 | 2 | 1.5 | 2 | 2.2 | 88 | 25 | 758 | 0.069 | 2 |
| GT5aNS5B, Con-1 | 350 | 0.023 | 3 | 0.62 | 0.5 | 1.8 | 2 | 0.16 | 0.2 | 0.2 | 8 | 5 | 152 | 0.0032 | 0.1 |
a
The susceptibilities of the chimeric replicon cell lines to HCV inhibitors were evaluated in the reporter replicon assay. Cells were exposed to compounds for 3 days before RLuc activity was determined. Results represent the averages of duplicate values. FC, fold change in EC50 over that of the wild-type Con-1 replicon.