Table 3.
Activity of GSK5852 and HCV-796 against genotype 1a and 1b NS5B variants
| Genotype and amino acid change | Mean replication capacity ± SD (n) | GSK5852 EC50 (95% confidence interval) (nM) | n | HCV-796 EC50 (95% confidence interval) (nM) | n |
|---|---|---|---|---|---|
| Genotype 1a | |||||
| None | 100% | 0.73 (0.65–0.82) | 13 | 11.9 (10.0–14.0) | 126 |
| C316F | NDb | 16.4 (14.6–18.6) | 8 | 8,035 (7,080–9,120)a | 2 |
| C316Y | 7% ± 3% (3) | 3.25 (2.61–4.04) | 8 | 1,900 (1,300–2,800) | 38 |
| S365L | 2% ± 1% (3) | 226 (193–266) | 4 | 400 (2.4–66,000) | 4 |
| S368F | 1% ± 1% (3) | 670 (557–806) | 8 | 9,000 (7,400–11,000)a | 2 |
| S368Y | 3% ± 3% (3) | 278 (260–299) | 4 | 310 (23–4,100) | 6 |
| L392F | 180% ± 10% (3) | 1.83 (1.47–2.27) | 4 | 10.8 (9.0–13.0) | 4 |
| Genotype 1b | |||||
| None | 100% | 0.83 (0.76–0.90) | 47 | 7.1 (6.6–7.6) | 69 |
| C316F | 7% ± 2% (3) | 3.78 (1.64–8.73) | 4 | 2,460 (2,000–3,030) | 8 |
| C316Y | 7% ± 8% (3) | 1.4 (0.81–2.40) | 8 | 400 (320–510) | 16 |
| S365A | 72% ± 32% (3) | 0.31 (0.25–0.38)a | 2 | 440 (340–560) | 10 |
| S365F | 14% ± 10% (3) | 28,300 (12,000–66,700) | 4 | ND | 0 |
| S365L | 6% ± 2% (3) | 110 (97.1–126) | 8 | >5,000 | 1 |
| S365T | 9% ± 4% (3) | 4.2 (2.91–6.19) | 8 | 1,100 (420–2,900) | 11 |
| C445F | 171% ± 123% (3) | 1.85 (1.07–3.19) | 4 | 43 (34–54) | 10 |
| C316Y/C445F | ND | 22.4 (19.4–25.8) | 4 | 1,600 (590–4,200) | 6 |
a
Range is for values with n of <4.
b
ND, not determined.