TABLE 4

In vitro activity of glecaprevir or pibrentasvir against amino acid substitutions in GT1a and GT3a repliconsa

HCV GT and variantMean glecaprevir EC50 ± SD (nM)Mean pibrentasvir EC50 ± SD (pM)Fold change in EC50
1a
    NS3
        Wild type0.21 ± 0.08
        Q80K0.19 ± 0.050.9
        A156VNA
    NS5A
        Wild type0.72 ± 0.45
        Q30R1.2 ± 0.621.7
        L31M0.76 ± 0.111.1
        H58D0.80 ± 0.171.1
        Y93N5.1 ± 2.17.0
        Q30R + L31M2.1 ± 0.793.0
        Q30R + Y93N94.6 ± 15.5131
        L31M + H58D16.6 ± 2.723
        Q30R + L31M + H58D1,227 ± 2771,704
3a
    NS3
        Wild typeb0.55 ± 0.17
        Y56HNA
        Q80R11.5 ± 1.621
        A156G909 ± 3491654
        S166ANA
        S166T2.6 ± 0.584.7
        Q168L6.9 ± 1.713
        Q168R30.0 ± 10.454
        Y56H + S166ANA
        Y56H + Q168LNA
        Y56H + Q168R763 ± 3631387
        S166A + Q168(K/L/R)NA
    NS5A
        Wild type0.65 ± 0.16
        M28GNA
        A30K0.71 ± 0.181.1
        L31FNA
        Y93H1.5 ± 0.192.3
        A30K + Y93H45.1 ± 2.369
        L31F + Y93HNA
  • a EC50, 50% effective concentration. Fold change was determined relative to the wild-type value. NA, not available due to low replication efficiency of the replicon containing the amino acid substitution; SD, standard deviation.

  • b The wild-type replicon has S166 in NS3.