Table 3.
Effects of genotype 1b HCV NS5A amino acid substitutions on DBPR110 potency
| Amino acid substitution(s) | Replication efficiency (%)a | EC50 (pM)a | Resistance at EC50 (n-fold) | EC90 (pM)a | Resistance at EC90 (n-fold) |
|---|---|---|---|---|---|
| None (parental) | 100 | 1.5 ± 0.6 | 1 | 4.2 ± 2.1 | 1 |
| P58S | 42 ± 10 | 38 ± 14 | 25 | 64 ± 11 | 15 |
| P58T | 40 ± 15 | 243 ± 40 | 162 | 1303 ± 219 | 310 |
| P58L | 19 ± 8 | 564 ± 194 | 376 | 2731 ± 909 | 650 |
| Y93N | 8 ± 3 | 3,821 ± 1,677 | 2,547 | 13,305 ± 3,416 | 3,168 |
| Y93H | 8 ± 4 | 1,408 ± 293 | 939 | 7,337 ± 2,206 | 1,747 |
| Y93C | 9 ± 6 | 78 ± 40 | 52 | 177 ± 62 | 42 |
| V153 M | 70 ± 17 | 1.3 ± 0.5 | 1 | 4.1 ± 1.9 | 1 |
| M202L | 106 ± 37 | 2.1 ± 0.6 | 1 | 5.0 ± 1.4 | 1 |
| M265V | 87 ± 23 | 2.0 ± 0.9 | 1 | 5.1 ± 1.7 | 1 |
| V153M M202L M265V | 157 ± 52 | 1.1 ± 0.5 | 1 | 3.1 ± 1.1 | 1 |
| Y93N V153M M202L M265V | 16 ± 4 | 27,326 ± 12,349 | 18,217 | 98,912 ± 30,548 | 23,550 |
| Y93H V153M M202L M265V | 32 ± 10 | 8,736 ± 2,370 | 5,824 | 37,710 ± 6,970 | 8,979 |
a
Means ± standard deviations determined from transient transfection assays (n ≥ 3).