Figure 3.

Substitution networks emerging in NS5A domain I under treatments with NS5A inhibitors. (A–E) ED43 full-length cultures were treated with ombitasvir (A), elbasvir (B), ledipasvir (C), velpatasvir (D) and pibrentasvir (E). (A–C): Inhibitor concentration: 100x-EC₅₀. (D) Initial concentration: 10x-EC₅₀; increased to 100x-EC₅₀ at day 28. (E) Treatment initiated at 5x-EC₅₀, then increased to 10x- and 100x-EC₅₀ at days 33 and 40, respectively. (F) Efficacy of pibrentasvir against ED43 full-length DAA escape viruses. Values are means of triplicates±SEM. (G) EC₅₀ values and 95% CI of indicated escape viruses were calculated from data shown in (F) and online supplemental figure 6. (H) Fitness of ED43 recombinant viruses harbouring NS5A RASs. ^#The data were obtained from the experiment shown in figure 2F. For details, see figure 2 legend. RAS, resistance-associated substitution; SEM, standard error of the mean.