Fig. 5. Nirmatrelvir and GC376 react differently to mutants.
(A) Gain-of-signal assay results are shown for single mutants Y54C and L167F versus wild-type tested with GC376 and nirmatrelvir (Y54C: n = 4, L167F: n = 3 biologically independent replicates per condition). (B) GC376 (PDB: 7k0g) and nirmatrelvir (PDB: 7vh8) 3CLpro crystal structures are shown with GC376 in green (and colored by heteroatom) and nirmatrelvir in light blue (and colored by heteroatom) and proximal residues in orange (within zone of 5 Å). Compound to residue distances are shown with dotted purple lines. (C) Fitting of gain-of-signal assay results are shown for single mutants Y54C and L167F versus wild-type tested with GC376 and nirmatrelvir. (D) Fitting of gain-of-signal assay results are shown for single mutant Q192R versus wild-type tested with GC376 and nirmatrelvir. Data in (C and D) are presented as the SD of n = 4 biologically independent replicates per condition.