Fig. 1. Identification of nirmatrelvir resistance in Vero E6 cells.
a, Changes in IC50 during passaging of SARS-CoV-2 with nirmatrelvir. Vero E6 cells were infected in triplicate with SARS-CoV-2 (USA-WA1/2020) and passaged to fresh cells every 3 days for 30 passages (Methods). b–d, Validation of nirmatrelvir resistance for the indicated passage from each of the three lineages (A (b), B (c) and C (d)). e, Inhibition of passage 30 viruses from each lineage by remdesivir. f, Mutations in 3CLpro found in the indicated passages from each lineage. Dots indicate WT at that residue. Mutations are shaded according to frequency. g, Residues mutated with passaging in Vero E6 cells overlaid onto the 3CLpro structure with nirmatrelvir bound. The Cα of each mutated residue is denoted by a red sphere. The 3CLpro–nirmatrelvir complex was downloaded from PDB under accession code 7VH8. a–e, Error bars denote mean ± s.e.m of four technical replicates.