Table 2. In Vitro Potency of the Novel Prodrugs and BCV against Various DNA Viruses (Virus Strain Specified in Parentheses), Compared to a Virus-specific Positive Controla.
| +control | BCV | NPP-662 | NPP-663 | NPP-664 | NPP-666 | NPP-667 | NPP-669 | ||
|---|---|---|---|---|---|---|---|---|---|
| ADV53 | EC50 | 6.64 ± 4.79 | 0.02 ± 0.01 | 10.79 ± 17.45 | 0.01 ± 0.01 | 0.33 ± 0.30 | 0.01 ± 0.01 | 0.24 ± 0.16 | 0.01 ± 0.08 |
| (Adenoid 75) | SI | >23 | 46 | >5 | 83 | >152 | 84 | 180 | 74 |
| HSV11 | EC50 | 0.96 ± 0.19 | 0.03 ± 0.02 | 3.18 ± 3.78 | 0.07 ± 0.04 | 2.38 ± 2.90 | 0.01 ± 0.01 | 1.47 ± 1.73 | 0.02 ± 0.01 |
| (E-377) | SI | >156 | >33 | >16 | 149 | >21 | 1159 | >34 | 469 |
| HSV21 | EC50 | 0.38 ± 0.33 | 0.02 ± 0.01 | 0.01 ± 0.01 | 0.29 ± 0.13 | 0.29 ± 0.13 | 0.01 ± 0.01 | 0.29 ± 0.17 | 0.14 ± 0.23 |
| (G) | SI | >395 | >50 | >98 | >3950 | >172 | 498 | >172 | >14 |
| VZV1 | EC50 | 3.24 ± 0.26 | 0.005 ± 0.005 | 1.01 ± 0.22 | 0.02 ± 0.01 | 0.69 ± 0.54 | 0.01 ± 0.01 | 0.03 ± 0.03 | 0.007 ± 0.01 |
| (Ellen) | SI | >46 | 114 | >50 | 25 | 72 | 23 | 1069 | 31 |
| HCMV2 | EC50 | 1.63 ± 0.69 | 0.001 ± 0 | 0.07 ± 0.02 | 0.008 ± 0.01 | 0.017 ± 0.01 | <0.01 ± 0.01 | 0.01 ± 0.01 | <0.01 ± 0.01 |
| (AD169) | SI | >92 | 540 | >714 | 74 | 1821 | >19 | >3000 | >19 |
| *HCMV3 | EC50 | 0.15 | ND | 0.06 | <0.0003 | 0.004 | <0.0003 | 0.003 | <0.0003 |
| (GDGRK17) | SI | >1034 | ND | >17 | >2772 | >250 | >2753 | >333 | >2209 |
| **MCMV2 | EC50 | 8.10 ± 11 | 0.0041 ± 0.0041 | 0.59 ± 0.58 | 0.0015 ± 0.0016 | 0.056 ± 0.064 | 0.00028 ± 0.00003 | 0.36 ± 0.46 | 0.00046 ± 0.00023 |
| (Smith) | SI | >19 | >244 | >2 | >667 | >18 | >3571 | >3 | >2174 |
| EBV3 | EC50 | 10.10 ± 3.44 | 0.09 ± 0.09 | 9.94 ± 13.25 | 14.78 ± 25.52 | 3.81 ± 3.04 | 0.14 ± 0.11 | 5.17 ± 7.32 | 0.08 ± 0.07 |
| (Akata) | SI | >10 | >11 | >5 | >3 | >13 | 241 | >10 | 356 |
| HHV-6B3 | EC50 | 7.09 ± 3.59 | 0.03 ± 0.02 | 24.01 ± 15.25 | 0.09 ± 0.12 | 4.23 ± 5.00 | 0.02 ± 0 | 7.22 ± 9.80 | <0.02 ± 0 |
| (Z29) | SI | 10 | 16 | >2 | 4 | 10 | 4 | >7 | >4 |
| HHV-83 | EC50 | 1.50 ± 0.70 | 0.001 ± 0 | 0.53 ± 0.42 | 0.02 ± 0.01 | 0.03 ± 0.01 | 0.03 ± 0.02 | 0.03 ± 0.01 | 0.01 ± 0.01 |
| (BCBL-1) | SI | >67 | 690 | >94 | 51 | >1667 | 35 | >1667 | 89 |
| **JC virus3 | EC50 | 18.40 ± 16 | 0.35 ± 0.26 | 0.53 ± 0.66 | 0.075 ± 0.007 | 4.2 ± 4.6 | 0.05 ± 0.03 | >25.5 ± 35 | 0.07 ± 0.05 |
| (MAD-4) | SI | >8 | >3 | 48 | 13 | >6 | 17 | 1 | 14 |
| **BK virus3 | EC50 | 5.8 ± 3.9 | 0.005 ± 0.007 | 0.43 ± 0.59 | 0.035 ± 0.02 | 0.38 ± 0.07 | 0.09 ± 0.01 | 0.02 ± 0 | 0.01 ± 0.01 |
| (Gardner) | SI | >26 | 180 | >59 | 34 | 67 | 8 | 1225 | 70 |
| *vaccinia3 | EC50 | 14.6 | ND | ND | ND | ND | 25.75 | ND | 8.95 |
| (Copenhagen) | SI | >10 | ND | ND | ND | ND | >2 | ND | >6 |
a
Controls: 1acyclovir, 2ganciclovir, and 3CDV. EC50: μM; mean of 3 replicates, unless otherwise stated. *Single replicate and **mean of 2 replicates. ND: not determined.