Figure 1.

Schematic overview of the drug combination study. Nude mice were infected and treated as described in the text and summarized in Table 2. Survival was assessed (Figure 2; Supplementary Table 1) and lung virus titers were measured (Table 3; Supplementary Table 2). We then selected 264 virus samples (Supplementary Table 3) for further analysis, amplified them in Madin-Darby canine kidney (MDCK) cells, and determined their sensitivity to oseltamivir carboxylate (OS-C), laninamivir (LA), and favipiravir (FA) (Supplementary Table 4). For 19 viruses that were resistant to OS-C and LA (Table 4), we performed plaque assays, isolated 6 viral plaques each, determined the neuraminidase (NA) sequences by Sanger sequencing, and tested their sensitivity to OS-C, LA, and FA (Supplementary Table 5).