Table 3.
QRS compounds: Summary of activity against drug-resistant variants of human cytomegalovirus a.
| HCMV Resistance Genotype | UL97-M460I | UL97-T409M | UL97-H411Y | UL97-C480F | UL97-C592G |
| Reported phenotype b | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV |
| R-high | R-low | S | R-low | R-high | S | R-low | R-high | S | R-int | R-high | S | R-int | S | S | |
| Measured EC50 ref. drugs | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV |
| [103 × nM] | 9.24 ± 3.3 | 0.01 ± 0.0 | 0.07 ± 0.0 | 1.98 ± 0.2 | >30.0 ± 0.0 | 0.26 ± 0.0 | 3.76 ± 0.6 | 21.02 ± 4.6 | 0.42 ± 0.0 | 10.52 ± 2.2 | >30.0 ± 0.0 | 0.40 ± 0.1 | 4.67 ± 1.1 | 0.77 ± 0.0 | 0.40 ± 0.1 |
| Measured EC50 QRS | QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 |
| [nM] | 0.06 ± 0.0 | 0.13 ± 0.0 | 0.98 ± 0.1 | 0.11 ± 0.0 | 0.88 ± 0.6| 0.29 ± 0.0 | 0.20 ± 0.1 | 1.70 ± 0.8| 0.64 ± 0.4 | 0.40 ± 0.1 | 0.24 ± 0.1| 0.79 ± 0.3 | 0.60 ± 0.4 | 1.98 ± 1.5| 4.78 ± 3.4 |
| HCMV resistance genotype | UL97-L397R | UL97-F342S | UL97-H520Q | UL97-C603W | UL97-H469V |
| Reported phenotype | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV |
| S | R | S | R-high | R-int | S (for F342Y) | R-high | S | S | R-high | R-int | S | nd | nd | S | |
| Measured EC50 ref. drugs | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV | GVC | MBV | CDV |
| [103 × nM] | 2.24 ± 0.5 | 63.92 ± 4.4 | 0.34 ± 0.1 | 17.10 ± 1.5 | 20.31 ± 3.2 | 0.19 ± 0.1 | 10.74 ± 0.7 | 0.04 ± 0.0 | 0.10 ± 0.0 | 9.87 ± 1.0 | 1.53 ± 0.4 | 0.41 ± 0.1 | 1.22 ± 0.2 | 0.62 ± 0.2 | 0.18 ± 0.0 |
| Measured EC50 QRS | [ QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 | QRS6 | QRS7 | QRS9 |
| [nM] | 0.15 ± 0.1 | 0.008 ± 0.0| 0.67 ± 0.4 | 0.65 ± 0.6 | 1.98 ± 1.5 | 0.58 ± 0.4 | 0.73 ± 0.4 | 1.97 ± 2.0 | 0.06 ± 0.0 | 0.17 ± 0.1 | 7.38 ± 3.4 | 0.82 ± 0.1 | 0.03 ± 0.0 | 0.13 ± 0.0| 0.45 ± 0.1 |
a Recombinant HCMVs and antiviral test systems were described by our group elsewhere [44,55,57,62]. b Phenotypes of viral drug resistance were described by other researchers before [75]: R-high, high-level drug resistance; R-int, intermediate-level drug resistance; R-low, low-level drug resistance; S, drug sensitivity; nd, not determined. Colors indicate the phenotypes of drug resistance/sensitivity all analyzed viral mutants (red), as given by previous reports (upper blue) and EC50 values measured in this study (lower blue).