TABLE 5.
Genotypic and phenotypic analysis of GT1b patient viral isolatesa
Dose (mg) | GT or patient | Nadir (h) | NS5A RAM(s) at baseline, first 100 aa (%) | NS5A RAM(s) at nadir, first 100 aa (%) | EDP-239 EC50 (nM)c |
||
---|---|---|---|---|---|---|---|
Baseline | Nadir | Fold change | |||||
GT1b (Con1) | Reference | Reference | 0.003 | ||||
10 | 5404 | 72 | Y93H(4) | L28M(32), L31F(22), P58S(46), Y93H(98) | 0.002 | 0.454 | 272 |
5409 | 24 | 0.002 | 0.002 | 1 | |||
30 | 5405 | 12 | 0.004 | 0.004 | 1 | ||
5413b | 312 | L31M(34)/V(27), P58S(1), A92K(2), Y93C(6)/H(33)/N(2) | 0.003 | 0.071 | 25 | ||
5414b | 72 | Y93H(99) | R30Q(7), L31V(7), Y93H(99) | 1.2 | 3.2 | 3 | |
100 | 5402 | 24 | R30Q(76) | R30Q(17), Q62P(51), Y93C(1) | 0.004 | 0.003 | 1 |
5406 | 48 | 0.002 | 0.002 | 1 | |||
5410 | 12 | 0.002 | 0.002 | 1 | |||
200 | 5403 | 96 | P58S(99) | R30H(53), Y93H(99) | 0.002 | 1.8 | 809 |
5408 | 24 | Y93C(8) | 0.002 | 0.003 | 1 | ||
5411 | 12 | R30Q(100), Q62R(100) | R30Q(99), Q62R (99) | 0.001 | 0.001 | 1 |
aa, amino acids.
The viral RNA levels at nadir viral loads for patients 5413 and 5414 were below 1,000 IU/ml, and the sequence could not be amplified; 72 h was selected for patient 5414 and day 14 for patient 5413.
n = 2 biological replicates.