TABLE 3.
Effects of NS5A amino acid substitutions on BMS-790052 potency for genotype 1b
| Amino acid substitutiona | EC50 (pM)b | Fold resistance | Replication level (%) |
|---|---|---|---|
| None (parent) | 2.6 ± 0.3 | 1 | 100 |
| L23F | 1.5 ± 0.2 | 1 | 39 ± 9 |
| L28M | 4.1 ± 1.1 | 2 | 121 ± 54 |
| L28T | 52 ± 14 | 20 | 13 ± 5 |
| ΔR30 | NDd | NDd | None |
| R30E | 15.6 ± 8.1 | 6 | 11 ± 2 |
| R30Q | 1.5 ± 0.3 | 1 | 92 ± 2 |
| L31F | 12.6 ± 1.2 | 5 | 146 ± 44 |
| L31M | 8.4 ± 1.9 | 3 | 99 ± 23 |
| L31Vc | 61 ± 15 | 23 | 145 ± 44 |
| P32L | 44.7 ± 21 | 17 | 18 ± 6 |
| F37L | 1.7 ± 0.2 | 1 | 138 ± 28 |
| Q54H | 3.2 ± 0.5 | 1 | 83 ± 18 |
| P58H | 2.2 ± 0.5 | 1 | 103 ± 23 |
| P58S | 2.3 ± 0.4 | 1 | 121 ± 18 |
| Y93Hc | 49.2 ± 12.8 | 19 | 20 ± 7 |
| Y93N | 73.5 ± 5.5 | 28 | 21 ± 6 |
| L23F + L31F | 33.8 ± 5.1 | 13 | 65 ± 5 |
| L23F + Y93H | 208.3 ± 36.9 | 80 | 8 ± 1 |
| ΔR30 + P32L | >1,000,000 | >384,615 | 9 ± 9 |
| R30Q + L31F | 234.1 ± 98.7 | 90 | 224 ± 39 |
| L31F + Y93H | 14,874.3 ± 1,762.9 | 5,721 | 29 ± 8 |
| L31M + Y93H | 10,989.4 ± 122.9 | 4,227 | 36 ± 5 |
| L31V + P58S | 421.8 ± 69.8 | 162 | 82 ± 2 |
| L31V + Y93H | 21,674.5 ± 9,461.3 | 8,336 | 30 ± 10 |
| F37L + Y93H | 48.6 ± 6.3 | 19 | 34 ± 4 |
| Q54H + Y93H | 24.7 ± 6.4 | 10 | 22 ± 7 |
a
Substitutions identified in inhibitor-treated replicon cell lines are indicated in bold. Others are theoretical mutations. All replicons contain a S2204I adaptive mutation.
b
Mean ± standard deviation, determined in transient transfection assays (n ≥ 3).
c
Data were taken from the work of Gao et al. (6).
d
ND, not determined.