TABLE 3.
Antiviral activity of KAY-2-41 against cidofovir and (S)-HPMPDAP-resistant CMLV and VACV
| Compound | EC50 (μM)a |
||||||||
|---|---|---|---|---|---|---|---|---|---|
| CML14 | CML14 A314Vb | CML14 A314V + A684Vb | CML1 | CML1 T831Ib | VACV-WR | VACV-WR A314Vb | VACV-WR A314V + A684Vb | VACV-WR T831Ib | |
| (S)-HPMPC | 8.6 ± 3.2 | 24.4 ± 12.4* | 49.4 ± 21.4* | 7.1 ± 3.0 | 9.6 ± 3.6 | 16.7 ± 9.3 | 64.7 ± 30.2** | 148.4 ± 23.0*** | 108.7 ± 42.1*** |
| (S)-HPMPDAP | 0.5 ± 0.1 | 14.6 ± 4.2*** | 17.4 ± 10.6* | 0.2 ± 0.1 | 4.1 ± 2.8** | 2.0 ± 1.1 | 17.3 ± 9.7*** | 53.0 ± 13.9*** | 31.3 ± 9.4*** |
| KAY-2-41 | 0.46 ± 0.22 | 0.22 ± 0.11 | 0.10 ± 0.01* | 0.29 ± 0.11 | 0.26 ± 0.13 | 0.77 ± 0.46 | 0.44 ± 0.24 | 0.20 ± 0.12* | 1.09 ± 0.35 |
a
EC50, 50% effective concentration, or the concentration of compound required to reduce the viral cytopathic effect by 50%. Data are shown as the means ± standard deviations of at least four independent experiments. Asterisks indicate where the EC50 differs significantly from that of the corresponding WT virus, as determined by an unpaired t test: *, P < 0.05; **, P < 0.01; ***, P < 0.001.
b
Drug-resistant recombinant viruses previously characterized (35) and bearing amino acid substitutions, i.e., A314V, A314V plus A684V, or T831I, in the viral DNA polymerase (E9L).