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. 2012 Jan;56(1):569–572. doi: 10.1128/AAC.05166-11

Table 2.

In vitro susceptibility of NS3 protease inhibitor-resistant HCV replicon molecular clones to BI 201335 and other HCV inhibitors

Varianta Change in susceptibility (EC50 fold change) tob:
BI 201335 MK-7009 TMC435 ITMN-191 Boceprevir Telaprevir IFN-α
WT GT 1a H77
    D168V 620 ± 180 1,000 ± 460 780 ± 170 86 ± 16 ND ND 0.8 ± 0.2
    R155K 360 ± 90 260 ± 22 43 ± 8 140 ± 41 4.2 ± 0.7 2.9 ± 1.3 0.8 ± 0.2
WT GT 1b CON-1
    A156V 150 ± 10 ND 160 ± 9 5.7 ± 2.1 5.2 ± 0.4 >74d 1.9 ± 0.2
    R155Q 60 ± 9 84 ± 62 1.6c 19 ± 2.8 1.4c 2.5c 0.9 ± 0.2
    R155K 350 ± 14 220e 30c 447c 4.0f 10f 0.6 ± 0.2
    A156T 270 ± 98 76 ± 32 44c 4 ± 1.2 85f >30 1.2 ± 0.4
    D168G 80 ± 30 ND 4.4c 8.1c 0.4c ND 0.8 ± 0.1
    D168A 690 ± 332 220 ± 12 594c 30 ± 3.2 0.7c 0.4c 1.5 ± 0.5
    D168V 970 ± 256 560 ± 120 1,140 ± 570 50 ± 10 0.7 ± 0.1 0.5 ± 0.1 0.9 ± 0.4
    V36M 2.1 ± 0.5 2.0 ± 0.7 2.7 ± 0.5 2.1 ± 0.4 2.0 ± 0.4 7.0d 0.8 ± 0.2
    T54A 0.9 ± 0.2 0.6 ± 0.3 0.9 0.5 ± 0.2 6.0f 6.3d 0.9 ± 0.2
    T54S 3.5 ± 0.7 ND 1.2c 1.2 ± 0.5 5.0 ± 0.07 3.0 0.9 ± 0.2
    Q80K 2.2 ± 0.1 2.9 ± 0.2 14 ± 1.3 2.3 ± 0.3 1.0 ± 0.1 0.9 ± 0.04 1.0 ± 0.1
    Q80L 1.2 ± 0.2 1.5 ± 0.1 1.9 ± 0.2 1.3 ± 0.2 1.0 ± 0.06 1.0 ± 0.04 1.0 ± 0.1
    Q80N 0.6 ± 0.1 0.8 ± 0.2 0.7 ± 0.04 0.7 ± 0.2 ND 0.5 ± 0.1 0.8 ± 0.3
    Q80R 2.6 ± 0.5 2.6 ± 0.3 15 ± 0.7 3.1 ± 0.5 1.0 ± 0.2 0.9 ± 0.04 0.9 ± 0.2
a

WT, wild type.

b

EC50 values were determined after 72 h of incubation with serial dilution of the indicated inhibitor and quantified by real-time reverse transcription-PCR (RT-PCR) for R155Q, A156T, D168A, and D168G variants (10). All other EC50s were obtained from luciferase reporter replicons in 72-h assays. Fold change was calculated as follows: EC50 for the variant/EC50 for the WT. For each condition, the fold change represents the mean ± standard deviation (SD), which was calculated from at least 3 independent experiments. Replicon variants in boldface type represent those selected in replicon colonies resistant to BI 201335. Values in italic type are from published results. ND, not determined.

c

Published value obtained from reference 12.

d

Published value obtained from references 21 and 29.

e

Published value obtained from reference 13.

f

Published value obtained from reference 25.