Table. Inhibitory activity of selected compounds against replication of poliovirus Sabin strains 1, 2, and 3 in HeLa cells, as determined by a CPE reduction assay*.
| Compound | EC50 (µmol/L) |
Toxicity (CC50;µmol/L) | TI (min–max) | ||
|---|---|---|---|---|---|
| PV1 | PV2 | PV3 | |||
| Capsid binders | |||||
| Pirodavir analog (R78206) | 0.76 ± 0.18 | 0.22 ± 0.19 | 0.11 ± 0.10 | 27 ± 34 | 35–245 |
| Pleconaril | >100 | 1.1 ± 0.6 | 0.22 ± 0.15 | 66 ± 6 | <0.66–300 |
| Pirodavir (R77975) |
10 ± 1 |
1.7 ± 0.1 |
0.56 ± 0.03 |
>100 |
>10–>179 |
| Protease inhibitors | |||||
| Rupintrivir | 0.022 ± 0.028 | 0.041 ± 0.024 | 0.0052 ± 0.0046 | >100 | >2,439–>19,231 |
| Compound 1 |
0.26 ± 0.24 |
0.31 ± 0 .21 |
0.060 ± 0 .000 |
>100 |
>322–>1,667 |
| 3A inhibitor | |||||
| Enviroxime |
0.2 ± 0.25 |
0.056 ± 0.020 |
0.035 ± 0.029 |
58 ± 6 |
290–1,657 |
| Nucleoside analogs | |||||
| Ribavirin | 57 ± 13 | 64 ± 4 | 55 ± 7 | >100 | >1.6–>1.8 |
| 2'-C-methylcytidine† | 15 ± 18 | 29 ± 27 | 3.9 ± 2.3 | >100 | >3.4–>26 |
| 2'-C-methyladenosine | 5.5 ± 0.0 | 5.6 ± 0.1 | 5.4 ± 0.4 | 84 ± 0 | 15 |
| 4’-azidocytidine |
>100 |
>100 |
>100 |
>100 |
><1 |
| 2C inhibitors | |||||
| HBB | 300 ± 68 | 225 ± 128 | 295 ± 88 | >400 | >1.3–>1.8 |
| MRL-1237 |
5.3 ± 0.3 |
4.6 ± 1.4 |
3.8 ± 2.5 |
>100 |
>19–>26 |
| Unknown target | |||||
| MDL-860 | 6.0 ± 1.6 | 3.6 ± 2.2 | 2.2 ± 1.5 | >100 | >17–>45 |
*CPE, cytopathic effect; EC50, 50% effective concentration; CC50, 50% cytotoxic concentration; PV, poliovirus; TI, therapeutic index (CC50/EC50); min, minimum; max, maximum; HBB, 2-(α-hydroxybenzyl)-benzimidazole. †Valopicitabine (oral valine ester prodrug of 2′-C-methylcytidine).