TABLE 3.
Genotypes and susceptibility phenotypes of recombinant CMV strains
| Strain | Genotype | GW275175X |
Letermovir |
Tomeglovir |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EC50a | SDb | No. of replicatesc | Fold changed | EC50 | SD | No. of replicates | Fold change | EC50 | SD | No. of replicates | Fold change | ||
| 4190 | UL56 wild type | 1.1 | 0.28 | 107 | 3.8 | 0.86 | 100 | 0.44 | 0.07 | 123 | |||
| 4272 | UL89 wild type | 1.1 | 0.28 | 112 | 3.8 | 0.88 | 90 | 0.47 | 0.07 | 142 | |||
| Selected under GW275175X exposure | |||||||||||||
| 4274 | UL89 D344E | 10 | 2.4 | 113 | 9.4 | 7.0 | 1.1 | 20 | 1.8 | 0.81 | 0.16 | 47 | 1.7 |
| 4283 | UL89 C347S | 30 | 8.1 | 12 | 27 | 2.4 | 0.43 | 10 | 0.6 | 0.16 | 0.05 | 9 | 0.3 |
| 4339 | UL89 R351H | 9.3 | 1.2 | 10 | 8.5 | 2.6 | 0.33 | 11 | 0.7 | 0.17 | 0.03 | 10 | 0.4 |
| 4372 | UL56 E769D | 0.72 | 0.17 | 10 | 0.7 | 3.9 | 1.2 | 14 | 1.0 | 0.33 | 0.03 | 8 | 0.8 |
| 4349 | UL56 Q204R | 4.6 | 0.69 | 8 | 4.2 | 5.8 | 1.3 | 10 | 1.5 | 1.2 | 0.16 | 13 | 2.7 |
| 4357 | UL56 Q204R UL89 D344E | 22 | 2.8 | 8 | 21 | 9.4 | 2.3 | 9 | 2.5 | 2.5 | 0.22 | 10 | 5.8 |
| Selected under letermovir exposure | |||||||||||||
| 4263 | UL56 N232Y | 0.82 | 0.22 | 12 | 0.8 | 64 | 18 | 12 | 17 | 1.2 | 0.06 | 8 | 2.7 |
| 4249 | UL56 K258E | 0.72 | 0.15 | 8 | 0.7 | 52 | 16 | 12 | 14 | 0.14 | 0.01 | 8 | 0.3 |
| 4218 | UL56 F261L | 0.74 | 0.25 | 15 | 0.7 | 9.6 | 1.0 | 9 | 2.5 | 0.44 | 0.07 | 13 | 1.0 |
| 4313 | UL56 F261L UL89 D344E | 10 | 1.8 | 7 | 10 | 18 | 3.3 | 11 | 4.8 | 0.91 | 0.25 | 13 | 2.1 |
| 4271 | UL56 M329T | 0.90 | 0.28 | 12 | 0.8 | 17 | 5.7 | 12 | 4.5 | 0.46 | 0.11 | 10 | 1.1 |
| 4336 | UL56 M329T UL89 D344E | 11 | 2.7 | 8 | 10 | 30 | 6.1 | 10 | 8.0 | 0.98 | 0.12 | 10 | 2.2 |
| 4222 | UL56 E237D | 0.57 | 0.12 | 10 | 0.5 | 61 | 6.0 | 8 | 16 | 0.14 | 0.02 | 10 | 0.3 |
| 4314 | UL56 E237D UL89 D344E | 8.0 | 1.8 | 9 | 7.4 | 129 | 27 | 8 | 34 | 0.27 | 0.06 | 9 | 0.6 |
| 4284 | UL89 N320H | 4.6 | 0.97 | 10 | 4.2 | 7.0 | 0.44 | 7 | 1.8 | 3.0 | 0.24 | 11 | 6.5 |
| 4341 | UL89 M359I | 0.60 | 0.11 | 8 | 0.5 | 5.6 | 1.6 | 16 | 1.5 | 3.4 | 0.92 | 14 | 7.4 |
| Selected under tomeglovir exposure | |||||||||||||
| 4368 | UL89 I334V | 1.0 | 0.26 | 9 | 0.9 | 4.0 | 0.82 | 10 | 1.1 | 0.41 | 0.10 | 10 | 0.9 |
| 4367 | UL89 N329S | 0.75 | 0.20 | 8 | 0.7 | 7.7 | 2.2 | 13 | 2.0 | 6.9 | 0.63 | 11 | 15 |
| 4334 | UL89 T350M | 5.6 | 1.2 | 11 | 5.1 | 11 | 2.5 | 10 | 2.8 | 4.1 | 0.66 | 10 | 8.7 |
| 4323 | UL89 V362M | 0.69 | 0.12 | 7 | 0.6 | 4.7 | 1.1 | 8 | 1.2 | 46 | 3.7 | 11 | 98 |
| 4326 | UL89 H389N | 0.98 | 0.32 | 16 | 0.9 | 4.1 | 0.75 | 10 | 1.1 | 14 | 2.4 | 132 | 29 |
| 4369 | UL89 N405D | 0.72 | 0.21 | 17 | 0.7 | 3.9 | 0.61 | 12 | 1.0 | 6.9 | 0.54 | 12 | 15 |
| 4327 | UL89 I334V N405D | 0.71 | 0.18 | 10 | 0.6 | 4.5 | 0.82 | 12 | 1.2 | 5.6 | 0.59 | 9 | 12 |
| 4337 | UL56 L208M | 0.71 | 0.13 | 11 | 0.7 | 3.1 | 0.29 | 8 | 0.8 | 1.5 | 0.36 | 13 | 3.4 |
| 4330 | UL56 E407D | 0.99 | 0.14 | 8 | 0.9 | 5.1 | 0.63 | 7 | 1.3 | 2.7 | 0.16 | 9 | 6.0 |
| 4358 | UL56 H637Q | 1.0 | 0.17 | 10 | 0.9 | 3.4 | 0.48 | 7 | 0.9 | 0.89 | 0.09 | 10 | 2.0 |
| 4359 | UL56 V639M | 1.0 | 0.36 | 18 | 0.9 | 4.0 | 0.48 | 8 | 1.0 | 4.6 | 0.42 | 8 | 10 |
| 4356 | UL56 H637Q V639M | 0.91 | 0.16 | 8 | 0.8 | 4.6 | 1.0 | 13 | 1.2 | 7.5 | 1.0 | 10 | 17 |
| 4366 | UL56 L764M | 1.1 | 0.30 | 9 | 1.0 | 4.3 | 1.2 | 12 | 1.1 | 0.19 | 0.02 | 8 | 0.4 |
The mean concentration required for 50% SEAP yield reduction (data are in nanomolar for letermovir and micromolar for the other compounds).
Standard deviation of EC50 values.
Number of replicates of testing (over at least 4 setup dates).
Fold change in EC50 compared with that for the wild type (fold changes of >1.5-fold are shown in bold, and underlined data denote cross-resistance). Fold changes of 1.5 are significant at a P value of <0.0025; all fold changes of >1.6 are significant at a P value of <1 × 10−4.