TABLE 1.
Genotypes and drug susceptibility phenotypes of recombinant CMV strains evaluated in HFF cells
| Strain type and numbera | Variantb | Synguanol |
MBX1616 |
MBX2168 |
||||||
|---|---|---|---|---|---|---|---|---|---|---|
| EC50c (μM; mean ± SD) | nd | Ratioe | EC50 (μM; mean ± SD) | n | Ratio | EC50 (μM; mean ± SD) | n | Ratio | ||
| Baseline AD169-derived strains | ||||||||||
| T3261 | Wild type | 0.95 ± 0.20 | 12 | 0.81 ± 0.22 | 58 | 0.46 ± 0.13 | 61 | |||
| T3265 | Wild type | 1.05 ± 0.31 | 32 | 1.01 ± 0.26 | 40 | 0.46 ± 0.15 | 46 | |||
| UL97 mutants | ||||||||||
| T3362 | M460I | 4.92 ± 1.25 | 23 | 5.2 | 5.28 ± 1.45 | 39 | 6.5 | 1.78 ± 0.44 | 39 | 3.9 |
| T3346 | M460T | 4.76 ± 1.60 | 11 | 5.0 | 4.91 ± 1.42 | 8 | 6.1 | 1.84 ± 0.43 | 8 | 4.0 |
| T2259 | M460V | 4.76 ± 1.27 | 12 | 5.0 | 4.45 ± 0.69 | 7 | 5.5 | 1.08 ± 0.23 | 8 | 2.3 |
| T3324 | H520Q | 5.30 ± 1.30 | 11 | 5.6 | 5.57 ± 1.19 | 10 | 6.9 | 1.69 ± 0.32 | 12 | 3.7 |
| T3259 | C592G | 1.84 ± 0.56 | 11 | 1.9 | 2.84 ± 0.87 | 12 | 3.5 | 0.93 ± 0.18 | 10 | 2.0 |
| T3252 | A594V | 1.64 ± 0.45 | 7 | 1.7 | 2.19 ± 0.40 | 9 | 2.7 | 0.67 ± 0.19 | 10 | 1.5 |
| T2260 | L595S | 1.04 ± 0.24 | 12 | 1.1 | 2.41 ± 0.55 | 8 | 3.0 | 0.90 ± 0.29 | 10 | 2.0 |
| T3329 | C603W | 2.00 ± 0.48 | 9 | 2.1 | 2.57 ± 0.37 | 11 | 3.2 | 1.01 ± 0.14 | 11 | 2.2 |
| UL54 pol mutants | ||||||||||
| T4053 | T700A | 3.83 ± 0.80 | 8 | 3.6 | 3.87 ± 1.36 | 12 | 3.8 | 2.10 ± 0.69 | 9 | 4.6 |
| T4059 | A719V | 5.66 ± 1.78 | 13 | 5.4 | 4.29 ± 1.93 | 8 | 4.2 | 2.45 ± 0.72 | 6 | 5.3 |
| T3658 | E756D | 2.59 ± 0.48 | 7 | 2.5 | 3.48 ± 0.70 | 16 | 3.4 | 1.74 ± 0.37 | 12 | 3.8 |
| T3271 | A809V | 2.56 ± 0.69 | 7 | 2.4 | 3.23 ± 0.77 | 10 | 3.2 | 1.86 ± 0.41 | 10 | 4.0 |
| T3652 | M844V | 6.50 ± 1.65 | 6 | 6.2 | 6.31 ± 0.45 | 12 | 6.2 | 3.19 ± 0.70 | 14 | 6.9 |
| T4063 | K853R | 1.10 ± 0.20 | 12 | 1.0 | 1.09 ± 0.24 | 7 | 1.1 | 0.47 ± 0.13 | 8 | 1.0 |
| T3429 | A987G | 0.55 ± 0.17 | 10 | 0.5 | 0.52 ± 0.10 | 8 | 0.5 | 0.18 ± 0.06 | 8 | 0.4 |
| UL54 exo mutants | ||||||||||
| T4066 | D301N | 0.12 ± 0.03 | 11 | 0.12 | 0.14 ± 0.04 | 7 | 0.13 | 0.06 ± 0.02 | 7 | 0.12 |
| T3313 | N408K | 0.04 ± 0.01 | 7 | 0.04 | 0.04 ± 0.01 | 7 | 0.04 | 0.03 ± 0.01 | 9 | 0.06 |
| T3267 | F412L | 0.10 ± 0.03 | 9 | 0.09 | 0.18 ± 0.07 | 8 | 0.18 | 0.05 ± 0.01 | 10 | 0.10 |
| T3005 | P522A | 0.26 ± 0.08 | 8 | 0.24 | 0.29 ± 0.05 | 8 | 0.29 | 0.09 ± 0.03 | 16 | 0.20 |
a
Recombinant virus serial numbers used as identifiers.
b
Amino acid substitution in the indicated gene.
c
The mean drug concentration required to reduce supernatant SEAP reporter activity by 50% at 1 week.
d
Number of assay replicates.
e
Ratio of the mean EC50 to that of the matching baseline strain (T3261 for UL97 mutants and T3265 for UL54 mutants). Values in bold indicate a >5-fold change from the baseline strain.