TABLE 1.
Effect of maribavir on EC50s of other anti-CMV drugs
Cell type and strain | UL97 genotype | Drug A | Drug B (concn [μM]) | EC50 (μM) of drug A (no. of replicates)a | FIC | MBV ∑FICb | |
---|---|---|---|---|---|---|---|
HFF | |||||||
T2233 | WTc | GCV | None | 1.0 ± 0.4 (28) | |||
GCV | MBV (0.04) | 1.6 ± .76 (13) | 1.5 | >3.9 | |||
GCV | MBV (0.16) | 4.5 ± 1.2 (19) | 4.3 | >6.7 | |||
GCV | MBV (0.64) | 6.6 ± 3.3 (17) | 6.3 | >8.7 | |||
GCV | MBV (2.5) | 8.3 ± 2.3 (12) | 8.0 | >10 | |||
GCV | MBV (5) | 14 ± 4.5 (15) | 13 | >15 | |||
GCV | MBV (10) | 13 ± 3.0 (7) | 13 | >15 | |||
FOS | None | 45 ± 8.3 (15) | |||||
FOS | MBV (10) | 39 ± 7 (8) | 0.9 | 0.9 | |||
CDV | None | 0.26 ± 0.07 (14) | |||||
CDV | MBV (10) | 0.27 ± .18 (7) | 1.0 | 1.1 | |||
MBV | None | 13 ± 3.6 (16) | |||||
MBV | GCV (1) | >32 (6) | >2.4 | ||||
MBV | FOS (40) | 0.47 ± 0.3 (16) | 0.04 | ||||
MBV | CDV (0.3) | 0.41 ± 0.05 (5) | 0.03 | ||||
HEL cells | |||||||
T2233 | WT | GCV | None | 0.55 ± 0.18 (12) | |||
GCV | MBV (0.04) | 1.2 ± 0.19 (6) | 2.2 | 4.1 | |||
GCV | MBV (0.16) | 2.6 ± 0.89 (13) | 4.7 | 6.6 | |||
GCV | MBV (0.32) | 4.9 ± 1.0 (11) | 8.9 | 11 | |||
FOS | None | 39 ± 10 (7) | |||||
FOS | MBV (0.16) | 27 ± 9 (7) | 0.7 | 1.6 | |||
CDV | None | 0.36 ± 0.04 (6) | |||||
CDV | MBV (0.16) | 0.29 ± 0.12 (6) | 0.8 | 1.6 | |||
MBV | None | 0.10 ± 0.03 (51) | |||||
MBV | GCV (0.5) | 0.19 ± 0.01 (4) | 1.9 | ||||
MBV | FOS (40) | 0.09 ± 0.03 (7) | 0.9 | ||||
MBV | CDV (0.4) | 0.08 ± 0.00 (4) | 0.8 | ||||
T2264 | L397R (MBVr) | MBV | None | 24 ± 9.1 (7) | |||
GCV | None | 1.9 ± 0.73 (6) | |||||
GCV | MBV (10) | 1.9 ± 0.74 (4) | 1.0 | ||||
FOS | None | 31 ± 14 (7) | |||||
FOS | MBV (10) | 48 ± 13 (4) | 1.6 | ||||
CDV | None | 0.47 ± 0.09 (4) | |||||
CDV | MBV (10) | 0.45 ± 0.3 (6) | 1.0 | ||||
T2258 | C592G (low-grade GCVr) | MBV | None | 0.2 ± 0.04 (5) | |||
GCV | None | 2.5 ± 1.4 (5) | |||||
GCV | MBV (0.2) | 7.2 ± 1.1 (4) | 2.9 | ||||
T2260 | L595S (GCVr) | MBV | None | 0.25 ± 0.08 (5) | |||
GCV | None | 7.9 ± 3.2 (5) | |||||
GCV | MBV (0.2) | 8.6 ± 5.4 (7) | 1.1 |
EC50s are for drug A in the presence of drug B and are shown as the mean±the standard deviation.
Values of >4, defining drug antagonisms, are in bold.
The phenotype associated with the genotype is in parentheses.