Activities of benzimidazole nucleosides against HCMV isolates sensitive and resistant to TCRB and BDCRB

CompoundMean ± SD IC50 or IC90 (μM)a for virus isolateb:
Towne (wild type)B11 (UL89)D10 (UL89)C4 (UL56 + UL89)
TCRB2.8 ± 1.116 ± 4.917 ± 7.656 ± 31
BDCRB1.2 ± 0.7812 ± 6.77.3 ± 5.828 ± 7.4
5′-dTCRB0.58 ± 0.46c2.9 ± 0.5c3.1 ± 0.14c13d
5′-dBDCRB0.15 ± 0.001c
5′-dBDCRBe0.06 ± 0.013.0 ± 0.8
GCV1.5 ± 0.63.1 ± 0.2c4.6 ± 2.15.5 ± 3.2
  • a Results are from plaque reduction assays performed in duplicate with the indicated isolates of HCMV selected for resistance to TCRB, as described in the text. The 50% inhibitory concentration (IC50s) were calculated from three to six separate experiments with at least four drug concentrations each, unless marked otherwise.

  • b The genotype of each isolate is given in parentheses. The UL number specifies the gene with the mutation that confers resistance to TCRB; the UL89 mutation is D344E, and the UL56 mutation is Q204R (25). B11 and D10 are different isolates with the same mutation that results in resistance to TCRB, which we have described previously (25).

  • c The experiment was performed twice, in duplicate, by using at least four drug concentrations.

  • d The experiment was performed once, in duplicate, by using five drug concentrations.

  • e The results are presented as 90% inhibitory concentrations (IC90s) from two yield reduction experiments performed in duplicate or triplicate wells by using at least five drug concentrations.