TABLE 1.
In vitro serial passage of HRV 14 in the presence of rupintrivir
| Passage historya
|
Phenotypeb as EC50 (nM [fold change]) | Genotypec as amino acid substitutions | ||
|---|---|---|---|---|
| Passage no. | No. of days (cumulative) | >Fold EC50 (concn [nM]) | ||
| WT | 0 | 0 | 21 ± 11 | — |
| 1 | 6 | 3.5 (70) | ND | — |
| 2 | 11 | 3.5 (70) | ND | — |
| 3 | 14 | 5 (100) | 152 ± 108 (7)d | T129T/A, T131T/A, T143P/S |
| 4 | 17 | 10 (200 | 227 ± 124 (11)d | T129A, T131T/A, T143P |
| 5 | 22 | 20 (400) | 96 ± 16 (5)d | T129A, T131T/A, T143P |
| 6 | 27 | 20 (400) | ND | T129A, T131T/A, T143P |
| 7 | 33 | 30 (600) | ND | T129A, T131T/A, T143P |
| 8 | 40 | 40 (800) | ND | T129A, T131T/A, T143P |
| 9 | 48 | 60 (1,200) | ND | T129A, T131A, T143P, Y139Y/H |
| 10 | 55 | 90 (1,800) | 324 ± 170 (15)d | T129A, T131A, T143P, Y139Y/H |
| 11 | 65 | 90 (1,800) | 335 ± 60 (16)d | A121A/V, T129A, T131A, T143P, Y139Y/H |
| 12 | 72 | 90 (1,800) | 414 ± 92 (20)d | A121A/V, T129A, T131A, N132S, Y139Y/H, T143P |
HRV 14 was serially passaged for the indicated number of times (passage number) or days in the presence of increasing concentrations of rupintrivir, as indicated.
The results represent the means ± the standard deviations from three or more experiments, as determined by CPE assays as described in Materials and Methods. ND, not determined. Values in parentheses (fold change) represent the ratio of the EC50 value obtained for mutant HRV compared to the EC50 value obtained for WT HRV 14.
All amino acid substitutions in the 3C protease-coding region relative to an HRV 14 reference sequence are reported. —, no change relative to the reference sequence.
P ≤ 0.05 by comparison of antiviral susceptibility data between the indicated HRV variants and WT HRV.