Table 1. Effect of compound 17, rupintrivir (a 3C-protease inhibitor), and TP0219 (a glutathione-depleting compound) on the in vitro replication of CVB3 WT and reverse-engineered CVB3 variants in CPE reduction assays.
| Variant | Compound 17 | Rupintrivir | TP0219 | |||
|---|---|---|---|---|---|---|
| EC50 ± SD (μM) | RR | EC50 ± SD (μM) | RR | EC50 ± SD (μM) | RR | |
| WT | 0.7 ± 0.1 | - | 2.8 ± 0.5 | - | 16.7 ± 4 | - |
| VP1_Y75C | 7.9 ± 3.5 | 11** | ND | ND | ND | ND |
| VP1_F76C | 12 ± 1 | 18*** | 2 ± 1 | 0.7 | 2.3 ± 1 | 0.14 |
| VP1_T77M | 15 ± 4 | 21*** | ND | ND | >80 | >5 |
| VP1_E78G | 15 ± 2 | 21*** | 2 ± 0.03 | 0.7 | 19 ± 4 | 1.1 |
| VP1_A98V | 2.2 ± 0.3 | 3** | 3 ± 0.6 | 1.1 | 27 ± 6 | 1.6 |
| VP1_D133G | 28 ± 3 | 38*** | 3.4 ± 1 | 1.2 | 11 ± 1 | 0.7 |
| VP1_D155G | >40 | >57 | ND | ND | ND | ND |
| VP3_N235G | 1.0 ± 0.2 | 1.2 | ND | ND | ND | ND |
Data were obtained from at least three independent experiments.
*p < 0.005.
**p < 0.001.
***p < 0.0001 (unpaired t test).
Abbreviations: CPE, cytopathic effect; CVB, Coxsackievirus B; EC50, 50% effective concentration; ND, not determined; RR, relative resistance (EC50 of the mutant/EC50 of WT); WT, wild-type.