TABLE 2.
In vitro activities of GCV, PFA, BDCRB, cidofovir, and compound 1 against various cytomegalovirus isolates by the plaque reduction assay
| Isolate | Cell line | IC50 (μg/ml)a
|
||||
|---|---|---|---|---|---|---|
| GCV | PFA | BDCRB | Cidofovir | Compound 1 | ||
| AD 169 | Hs68 | 0.3 ± 0.05 | NDb | ND | 0.02 ± 0.003 | 0.09 ± 0.002 |
| AD 169 | MRC-5 | 2.2 ± 0.2 | ND | ND | 0.04 ± 0.006 | 0.11 ± 0.04 |
| P8c | MRC-5 | 2.5 ± 0.2 | ND | ND | 0.4 ± 0.04 | 0.2 ± 0.08 |
| C8704c | MRC-5 | 7.6 ± 0.6 | ND | ND | 0.14 ± 0.04 | 0.3 ± 0.07 |
| C8805-37c | MRC-5 | 12.0 ± 0.14 | ND | ND | 0.33 ± 0.07 | 0.32 ± 0.09 |
| D16c | MRC-5 | 28.0 ± 5.0 | ND | ND | 13.0 ± 0.0 | 0.4 ± 0.04 |
| AD 169 | HFF | ND | 29 | ND | 0.2 | 0.08 |
| Towne | HFF | 0.75 ± 0.25 | ND | 0.37 ± 0.14 | 0.16 ± 0.02 | 0.08 ± 0.0 |
| 4760recPolA1-1-1d | HFF | ND | 75 | ND | 0.2 | 0.2 |
| 1117r3-1-2d | HFF | ND | 35 | ND | 2.0 | 0.06 |
| D-10 C4d | HFF | ND | ND | >10 | 0.11 | 0.07 |
| MCMVe | 3T3-L1 | 1.0 ± 0.08 | ND | ND | 0.03 ± 0.004 | 0.05 ± 0.004 |
The IC50 was defined as the concentration of compound that resulted in a 50% reduction in plaque number compared to the number observed in control samples without drug. IC50s were calculated from dose-response curves obtained after linearly regressing the percent reduction of plaques against drug concentrations. For the experiments performed with the Hs68 fibroblasts, the data are presented as the averages of three or more experiments with the standard deviation. For the experiments performed with the MRC-5 and HFF cells, all dose-response curves for all HCMV strains were constructed by using seven and eight drug concentrations, respectively, in duplicate. For MCMV Smith, all dose-response curves were constructed by using six drug concentrations, in duplicate.
ND, not determined.
The following low-passage HCMV strains were used to infect MRC-5 cells: P8, which is GCV sensitive; C8704 and C8805-37, which are GCV resistant due to a UL97 phosphotransferase gene mutation (5, 44); and D16, which is GCV resistant through a mutation within the UL54 DNA polymerase gene (46).
HCMV 4760recPolA1-1-1 (genotype unknown) is PFA resistant and is derived from a clinical isolate (3), 1117r73-1-2 (genotype unknown) is cidofovir resistant and is derived from strain AD 169, and D-10 C4 (D344E and Q204R mutations within the UL89 and UL56 genes, respectively) is 2,5,6-trichloro-1-(β-d-ribofuranosyl)benzimidazole and BDCRB resistant and is derived from strain Towne (26).
Smith strain.