TABLE 2.
Effect of nucleoside analogs on wild-type and S282T replicons and NS5B polymerasesa
| Nucleoside analog | EC50 (μM) for HBI10A | EC50 (μM) for HBI10A-S282T | CC50 (μM) for MTS | IC50 (μM) for WT NS5BΔ55 | IC50 (μM) for S282T NS5BΔ55 |
|---|---|---|---|---|---|
| 7-Deaza-A (Tubercidin) | ≤0.4* | ND | 3 | ND | ND |
| 2′-C-Me-A | 0.25 ± 0.12 | 2.7 ± 0.6 | >100 | 1.9 ± 0.3 | >100 |
| 7-Deaza-2′-C-Me-A | 0.3 ± 0.16 | 10.1 ± 0.6 | >100 | 0.07 ± 0.1 | 25 ± 0.4 |
| 7-Deaza-2′-C-Me-G | >50 | ND | >100 | ND | ND |
a
The cytotoxic (MTS) and inhibitory effect on replicons was estimated in a 24-h cell culture assay. The effect on NS5BΔ55 was determined in the t500 polymerization assay. All data are averages for at least two experiments. *, toxicity observed at 0.4 μM concentrations and above. ND, not determined. A, adenosine; Me, methyl; G, guanosine.