TABLE 6

Antiviral activity of pibrentasvir against HCV replicons containing NS5A from genotypes 2 to 6 with amino acid substitutions that confer resistance to other NS5A inhibitors

HCV genotype and NS5A amino acid substitution(s)Pibrentasvir EC50a
Mean ± SD (pM)Fold change
2a
    Wild typeb0.99 ± 0.36
    T24A1.3 ± 0.301.3
    F28S1.2 ± 0.171.2
2b
    Wild typec1.2 ± 0.39
    L28F0.94 ± 0.270.8
    L31M1.5 ± 0.331.2
    L31V0.64 ± 0.200.5
3a
    Wild type0.65 ± 0.16
    M28T1.1 ± 0.021.7
    Y93H1.5 ± 0.192.3
4a
    Wild type0.78 ± 0.14
    L28V0.85 ± 0.231.1
    L30H1.1 ± 0.511.3
5a
    Wild type0.93 ± 0.20
    L28I0.98 ± 0.141.1
    L31F1.9 ± 0.112.1
    L31V0.75 ± 0.240.8
6a
    Wild typed1.0 ± 0.31
    L31V1.0 ± 0.381.0
    T58A1.4 ± 0.451.4
    T58N1.8 ± 0.711.8
  • a As determined in transient-transfection assays. Fold change is relative to the value of the respective wild-type replicon.

  • b The 2a wild-type replicon has M31 in NS5A.

  • c The 2b wild-type replicon has L31 in NS5A.

  • d The 6a wild-type replicon has L28 in NS5A.