Drug resistant variants near the binding pocket of DAAs in HCV NS3/4A protease (NS3: pink, NS4A: blue) in complex with asunaprevir. Near the binding pocket, amino acid positions associated with drug resistance towards the respective inhibitors are visualized in colored spheres. Spheres are colored in orange (only observed in HCV genotype (GT) 1a infected patients), in blue (only in GT1b), in red (GT1a and GT1b), in green (GT3a), in purple (GT1a, GT1b and GT4d), in black (GT1a, 1b and GT3a) and in cyan (GTs 1-4). For the visualization, PDB data of HCV protein structures were obtained from literature (NS5A: (1)) and the Protein Data Bank (NS3/4A: 3KEE and 4B76, NS5B: 4NLD and 4WTG).
Drug resistant variants in HCV NS5A dimer
HCV NS5A dimer in complex with daclatasvir.
Two units of HCV NS5A are colored by pink and orange, respectively. Near the binding pocket, amino acid positions associated with drug resistance towards the respective inhibitors are visualized in colored spheres. Spheres are colored in orange (only observed in HCV genotype (GT) 1a infected patients), in blue (only in GT1b), in red (GT1a and GT1b), in green (GT3a), in purple (GT1a, GT1b and GT4d), in black (GT1a, 1b and GT3a) and in cyan (GTs 1-4). For the visualization, PDB data of HCV protein structures were obtained from literature (PubMed link: [25365735] ).
Drug resistant variants in HCV NS5B polymerase
NS5B polymerase in complex with sofosbuvir and beclabuvir.
With different mechanisms of action, nucleotide inhibitors (e.g. sofosbuvir) and non-nucleoside inhibitors (e.g. beclabuvir) target the catalytic site and the allosteric site, respectively. Near the binding pocket, amino acid positions associated with drug resistance towards the respective inhibitors are visualized in colored spheres. Spheres are colored in orange (only observed in HCV genotype (GT) 1a infected patients), in blue (only in GT1b), in red (GT1a and GT1b), in green (GT3a), in purple (GT1a, GT1b and GT4d), in black (GT1a, 1b and GT3a) and in cyan (GTs 1-4). For the visualization, PDB data of HCV protein structures were obtained from the Protein Data Bank (NS5B: 4NLD and 4WTG).