TABLE 3.
GSK8853 efficacy against genotype 1b replicons containing NS4B sequence polymorphs
| Polymorph | EC50 (nM)a | Fold shift | 95% confidence interval (nM) | Variability at position |
|---|---|---|---|---|
| Wild type | 1.1 | 1.0 | 1.0–1.2 | |
| S2T | 1.0 | 0.9 | 0.60–1.48 | 87.7% S, 11.4% T |
| R44Q | 1.6 | 1.5 | 0.87–2.73 | 86.6% R, 11.7% Q |
| T45A | 1.1 | 1.0 | 0.65–1.88 | 10.9% T, 86.9% A |
| A48S | 0.7 | 0.6 | 0.44–1.18 | 40.9% A, 12.3% S |
| A48T | 1.7 | 1.5 | 0.83–2.34 | 40.9% A, 40.9% T |
| H94A | 37.2 | 33.8 | 20.1–39.5 | 46.2% H, 0.8% A |
| H94N | 37.7 | 34.2 | 34.7–41.0 | 46.2% H, 14.5% N |
| H94Q | 3.0 | 2.7 | 1.7–5.0 | 46.2% A, 1.9% Q |
| H94Rb | 52.6 | 47.8 | 41.9–66.0 | 46.2% A, 0% R |
| H94S | 29.7 | 27.0 | 22.7–38.8 | 46.2% A, 24.2% S |
| H94T | 138.5 | 125.9 | 70.6–270.1 | 46.2% A, 5.6% T |
| H94Y | 31.5 | 28.6 | 21.2–46.5 | 46.2% A, 6.4% Y |
| F98Lb | 27.1 | 24.6 | 23.6–31.2 | 94.7% F, 5.3% L |
| V105Lb | 6.6 | 6.0 | 6.0–7.2 | 97.8% V, 1.4% L |
| V105M | 179.0 | 162.7 | 159.4–200.9 | 97.8% V, 0.3% M |
| V157I | 1.0 | 0.9 | 0.54–1.72 | 81.6% V, 18.1% I |
| E161D | 19.4 | 17.6 | 14.3–26.2 | 89.7% E, 10.0% D |
| M162A | 8.0 | 7.3 | 5.2–12.1 | 69.9% M, 7.2% A |
| M162V | 40.7 | 37.0 | 20.4–68.0 | 69.9% M, 17.5% V |
| H94N_T45A | 52.0 | 47.3 | 35.6–74.8 | |
| H94N_I86V | 50.4 | 45.8 | 30.6–79.8 | |
| H94N_M162A | 149.3 | 135.7 | 81.5–261.4 | |
| H94N_V169I | 26.4 | 24.0 | 16.1–41.8 | |
| H94N_T45A_I86V | 34.4 | 31.3 | 25.5–45.3 | |
| H94T_Q93H | 433.2 | 393.8 | 325–569 | |
| H94T_F98L | 5,200.0 | 4,727.0 | 2,090–12,091 | |
| H94Y_R44Q | 25.4 | 23.1 | 19.2–33.2 | |
| H94Y_I86V | 155.6 | 141.5 | 128–187 | |
| H94Y_L109I | 955.0 | 868.2 | 397–1285 |
a
All replicons showed no change in potency in testing against NS5B inhibitor HCV-796 and/or NS3 inhibitor BILN-2061 as a control.
b
Data were originally reported in reference 7.