Fig. 2. Resistance profiling.
(A) Virus titers after passages shown in fig. S7 (N = 3). (B) Adaptation of influenza virus to baloxavir marboxil and NHC. Adaptation profile and amino acid frequencies of resistance mutations after deep-sequencing of baloxavir marboxil-experienced (N = 2) viruses (top panel). Deep-sequencing to identify mutation frequency (cut-off 5%) in influenza virus polymerase components after ten passages at 1 or 2 μM NHC or vehicle (lower panels). (C) C-to-U and G-to-A transition events after five and ten passages at 1 or 2 μM NHC relative to vehicle. Symbols show biological repeats, columns are means and error bars represent SDs. Statistical significance was explored by 2-way ANOVA and Dunnett’s post hoc test. (D) Re-passaging of NHC-experienced virus populations from (A) at 4 μM NHC. Symbols represent biological repeats, lines connect means. N = 4 for all NHC and vehicle-experienced virus populations in B-D.