Table 6.
Mutation(s) | EC50 fold change |
Replication fitness (% relative to WT) | |
---|---|---|---|
PSI-352938 | PSI-353661 | ||
Single | |||
C223H | ND | ND | 0.9 ± 0.49 |
C223Y | ND | ND | 2.2 ± 0.65 |
V321I | 1.3 ± 0.2 | 1.2 ± 0.2 | 126.6 ± 8.2 |
Multiple | |||
C223H/V321I | 2.3 ± 0.2 | 2.6 ± 0.3 | 21.9 ± 5.5 |
A15G/C223H/V321I | 4.8 ± 1.3 | 4.8 ± 0.8 | 10.1 ± 1.1 |
Effect of amino acid changes at positions 15, 223, and 321 was evaluated using the GT 1b Con1 replicon and a 4-day transient assay. Both replication fitness and sensitivity of the mutated replicon for PSI-352938 and PSI-353661 were examined. Values are averages ± standard deviations from at least three independent experiments performed in duplicate. ND, EC50 could not be determined because the levels of firefly luciferase were too low.