TABLE 3.
Activity of benzimidazole nucleoside 1311 against HCMV strains resistant to GCV, CDV, and PFA
| Compound | IC50 (μM) against the following virusesa:
|
||||
|---|---|---|---|---|---|
| 17517 | 48041 | AD169 | 4760 Rec Pol A | 1117 3-1-2 | |
| 1311 | 0.57 ± 0.23 | 0.82 ± 0.35 | 0.82 ± 0.10 | 0.87 ± 0.07 | 0.96 ± 0.07 |
| GCV | 3.2 ± 2.6 | 27 ± 8*b | 11.8 ± 3.9 | 14.3 ± 1.5 | 48.3 ± 5.5* |
| BDCRB | 0.46 ± 0.24 | 0.64 ± 0.05 | 0.58 ± 0.05 | 0.50 ± 0.11 | 0.53 ± 0.04 |
| PFA | NDc | ND | 50 ± 13 | 190 ± 10* | 52 ± 11 |
| CDV | ND | ND | 0.44 ± 0.04 | 0.40 ± 0.07 | 2.27 ± 0.67* |
Inhibition of HCMV plaque formation was measured by using at least six drug concentrations ranging from 100 to 0.05 μM. Data are presented as the means±SDs of IC50s determined in at least triplicate. HCMV strains 17517 (GCV sensitive) and 48041 (GCV resistant) are a matched pair of clinical isolates. Strain 48041 is resistant to GCV due to a mutation (L595S) in UL97 (K. K. Biron, personal communication). HCMV strains 4760 Rec Pol A (PFA resistant) and 1117 3-1-2 (CDV resistant) were derived from AD169 (wild type) and manifest their resistance to PFA or GCV and CDV due to mutations in the UL54 viral DNA polymerase gene (3).
*, P < 0.005 as determined by the Student's t test function of Microsoft Excel.
ND, not determined.