Extended Data Fig. 5: Structure of L50F/E166V in complexes with oridonin and oridonin-inhibition data.
From: Molecular mechanisms of SARS-CoV-2 resistance to nirmatrelvir
a, Overlay of WT Mpro-oridonin (PDB ID: 7VIC) and L50F/E166V-oridonin complex structures, WT Mpro is colored white, L50F/E166V mutant is colored marine. Oridonin in complex with WT Mpro is colored green, and the oridonin in complex with L50F/E166V is colored purple. Hydrogen bonds are shown as black dashes and their lengths are indicated in angstroms. b, Oridonin-inhibition data in enzymatic assays and cell-based assays, values are shown as fold change in IC50 value relative to inhibition of the WT Mpro by oridonin and fold change in EC50 relative to inhibition of the WT virus by oridonin. c, Representative curves for inhibition of recombinant SARS-CoV-2 carrying Mpro substitutions, data points are shown as mean ± standard error of the mean (SEM) for three technical replicates, EC50 values are given as mean ± SD for two biologically independent experiments. d-f, Dose-response curves of oridonin inhibiting Mpros in enzymatic assays, data points are shown as mean ± SD for four biologically independent replicates; d, Dose-response curves of oridonin inhibiting F140L, S144A, and E166V; e, Dose-response curves of oridonin inhibiting L167F and A193P; f, Dose-response curves of oridonin inhibiting T21I, T21I/E166V, and L50F/E166V.
