TABLE 3.
Antiviral activities of cidofovir, HPMPDAP, and siRNAs against different VACV-WR DNA polymerase mutants
| Compound | Antiviral activity (EC50)a (μM)
|
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|---|---|---|---|---|---|---|
| VACV-WR | VACV-WR DNA polymerase mutantsb
|
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| Single mutants
|
Double mutants
|
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| A314T | A684V | S851Y | A314T+A684V | A684V+S851Y | ||
| Cidofovir | 34 ± 5 | 139* ± 17 | 151* ± 13 | 151* ± 8 | >159* ± 0 | >159* ± 0 |
| HPMPDAP | 9 ± 2 | 59* ± 26 | 32* ± 5 | 21* ± 5 | 138* ± 13 | >157* ± 0 |
| siD5R-2 | 0.016 ± 0.01 | 0.005* ± 0.001 | 0.04* ± 0.01 | 0.003* ± 0.0003 | 0.018 ± 0.004 | 0.012 ± 0.004 |
| siG7L-1 | 0.011 ± 0.005 | 0.007* ± 0.003 | 0.07* ± 0.03 | 0.002* ± 0.0008 | 0.02 ± 0.01 | 0.03 ± 0.02 |
| siB1R-2 | 0.1 ± 0.0 | >0.1 ± 0.0 | >0.1 ± 0.0 | 0.02* ± 0.008 | >0.1 ± 0.0 | >0.1 ± 0.0 |
a
The EC50 of each compound represents the mean ± SD of the EC50s from at least three independent experiments. The 50% cytostatic concentrations of cidofovir and HPMPDAP were >159 μM, and that of each siRNA was >0.1 μM.
b
Mutations were identified in the VACV-WR DNA polymerase gene and were responsible for the resistance phenotypes observed with cidofovir (A314T, A684V, and A314T+A684V) and HPMPDAP (S851Y and A684V+S851Y). *, P < 0.05 (EC50s of siRNAs and compounds against VACV-WR DNA polymerase mutants differ significantly from EC50s against the wild-type strain) (Student's t test).