TABLE 1

EDP-239 potency against GT1 to GT6a subgenomic replicon cell lines and cytotoxicity in multiple cell types

HCV subgenomic replicon genotype and/or cell typeEC50 (nM) (mean ± SD)aEC50 fold shift in human serumCC50 (nM)cSelectivity index (CC50/EC50)
0% human serumb40% human serumb
1a (H77c)0.031 ± 0.0040.118 ± 0.0393.8>10,000>322,581
1b (Con1)0.007 ± 0.0020.019 ± 0.0062.7>10,000>1,428,571
2a (JFH1)6.5 ± 1.4
3a (S52)>50
1b/3a (FL)d5.01 ± 0.49
4a (ED43)0.063 ± 0.012
1b/4a (FL)d0.004 ± 0.001
1b/5a (100)d0.011 ± 0.002
1b/6a (FL)d0.394 ± 0.044
Vero, African Green Monkey kidney>10,000
MDBK, bovine kidney>10,000
MRC-5, human lung fibroblast>10,000
HEK293, human embryonic kidney>10,000
Raji, human lymphoma>10,000
  • a EC50s and standard deviations (SD) were calculated from at least two separate experiments using biological duplicates.

  • b Assay media with 0% and 40% human serum also include 10% fetal bovine serum. All replicons are stable replicon cell lines except genotypes 1b/5a and 1b/6a, which were transiently transfected.

  • c n = 12 biological replicates for each cell line. CC50 is the 50% cytotoxic concentration.

  • d Chimeric replicons expressing full-length NS5A (FL) or the first 100 amino acids of NS5A (100) cloned from patient isolates.