TABLE 10.
Activity of samatasvir against genotype 1a replicons bearing amino acid substitutions in NS3, NS4B, and NS5A
Region | Substitution | Mean fold change ± SD witha: |
Replicative capacity (% of WT ± SD)a | ||
---|---|---|---|---|---|
Samatasvir | Daclatasvir | IDX184 | |||
NS3 | T260A | 1.6 ± 0.3 | 1.7 ± 0.3 | 1.7 ± 0.2 | 300 ± 140 |
NS4B | E15G | 1.5 ± 0.1 | 1.6 ± 0.2 | 1.6 ± 0.1 | 264 ± 18 |
NS5A | K24E | 1.8 ± 0.5 | 1.8 ± 0.4 | 1.6 ± 0.2 | 79 ± 25 |
M28T | 150 ± 10 | 170 ± 20 | 1.06 ± 0.14 | 66 ± 7 | |
Q30E | 420 ± 80 | 2,900 ± 400 | 1.11 ± 0.14 | 119 ± 7 | |
Q30H | 24 ± 2 | 150 ± 30 | 1.07 ± 0.10 | 100 ± 2 | |
Q30K | 310 ± 100 | 750 ± 190 | 0.89 ± 0.17 | 100 ± 14 | |
Q30R | 10 ± 1 | 95 ± 22 | 1.04 ± 0.07 | 119 ± 7 | |
L31F | 68 ± 14 | 43 ± 9 | 1.06 ± 0.31 | 85 ± 4 | |
L31M | 310 ± 60 | 110 ± 30 | 1.04 ± 0.21 | 143 ± 32 | |
L31V | 420 ± 80 | 900 ± 180 | 1.33 ± 0.10 | 210 ± 8 | |
P32L | 170 ± 10 | 140 ± 20 | 0.89 ± 0.04 | 16 ± 3 | |
Y93C | 40 ± 5 | 290 ± 50 | 1.06 ± 0.16 | 92 ± 18 | |
Y93H | 4,400 ± 900 | 1,400 ± 500 | 1.05 ± 0.25 | 43 ± 4 | |
Y93N | 14,000 ± 3,000 | 7,800 ± 3,500 | 1.01 ± 0.25 | 60 ± 6 | |
E295G | 1.6 ± 0.2 | 1.6 ± 0.2 | 1.3 ± 0.1 | 132 ± 36 | |
R318W (GT 1a)b | RDc | RD | RD | 1.8 ± 0.8 | |
R318W (GT 1b)d | 1.7 ± 0.6 | 1.0 ± 0.1 | 0.75 ± 0.23 | 79 ± 4 |
n = 3. WT, wild type.
NS5A R318W substitution in the genotype 1a replicon.
RD, replication deficient.
NS5A R318W substitution in the genotype 1b replicon.