Table 4.
Effects of NS3 protease amino acid substitutions on asunaprevir and telaprevir potency in genotype 1b replicon transient-transfection assays
| Amino acid substitutiona | Asunaprevir |
Telaprevir |
Replication level (%) | ||
|---|---|---|---|---|---|
| EC50b (nM) | Fold increase in EC50 | EC50b (nM) | Fold increase in EC50 | ||
| WT | 0.86 ± 0.3 | 1 | 176 ± 41 | 1 | 100 |
| V36A | 1.6 ± 0.6 | 2 | 933 ± 281 | 5 | 124 |
| V36L | 0.65 ± 0.1 | 1 | 395 ± 19 | 2 | 77 |
| V36M | 1.9 ± 0.9 | 2 | 1,081 ± 224 | 6 | 59 |
| F43S | 3.2 ± 0.2 | 4 | 213 ± 36 | 1 | 79 |
| T54A | 0.35 ± 0.1 | 0.4 | 718 ± 31 | 4 | 101 |
| V55A | 0.79 ± 0.9 | 1 | 205 ± 4 | 1 | 4 |
| Q80K | 5.6 ± 1 | 6.5 | NDc | ND | 139 |
| Q80L | 0.86 ± 0.1 | 1 | 167 ± 14 | 1 | 98 |
| Q80R | 3.5 ± 0.9 | 4 | ND | ND | 102 |
| S122N | 0.7 ± 0.2 | 1 | 134 ± 34 | 1 | 194 |
| S122T | 1.2 ± 0.2 | 1 | 196 ± 11 | 1 | 205 |
| R155K | 23 ± 8 | 27 | 721 ± 75 | 4 | 54 |
| A156S | 5.9 ± 0.9 | 7 | 2,515 ± 624 | 15 | 120 |
| A156T | 5.4 ± 1 | 6 | >10,000 | >57 | 17 |
| A156V | 17 ± 2 | 20 | >10,000 | >57 | 3 |
| D168A | 109 ± 19 | 127 | 21 ± 4 | 0.1 | 37 |
| D168C | 56 ± 4 | 65 | 96 ± 30 | 1 | 25 |
| D168E | 67 ± 11 | 78 | 129 ± 7 | 1 | 25 |
| D168G | 13 ± 4 | 16 | 56 ± 12 | 0.3 | 29 |
| D168H | 85 ± 24 | 98 | 267 ± 105 | 2 | 12 |
| D168V | 241 ± 17 | 280 | 42 ± 7 | 0.2 | 29 |
| D168Y | 205 ± 29 | 238 | 71 ± 43 | 0.4 | 2 |
| V170A | 1.6 ± 0.4 | 2 | 699 ± 237 | 4 | 96 |
| V170I | 0.72 ± 0.01 | 1 | 184 ± 10 | 1 | 121 |
| V36M+R155K | 62 ± 29 | 72 | 4,483 ± 3,402 | 26 | 34 |
| F43S+D168E | 157 ± 30 | 183 | 147 ± 61 | 1 | 90 |
| Q41R+Q80R | 6.9 ± 0.4 | 8 | 229 ± 8 | 1 | 47 |
| Q41R+D168V | 202 ± 7 | 235 | 122 ± 33 | 1 | 20 |
| R155K+V170A | 18 ± 2 | 21 | 1,293 ± 117 | 7 | 84 |
a
WT, wild type. Substitutions associated with asunaprevir resistance selection in genotype 1b replicons are in bold.
b
Values are means ± standard deviations from ≥3 independent experiments.
c
ND, not determined.