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. 2023 Mar 29;9(13):eade8778. doi: 10.1126/sciadv.ade8778

Fig. 1. ∆P168 confers resistance to nirmatrelvir and ensitrelvir.

Fig. 1.

(A) Relative frequency of amino acid changes at P168, excluding proline (open circle), in SARS2 genomes (1 July 2022, GISAID database). (B) Cocrystal structures of SARS2 Mpro in complex with boceprevir (PDB: 6WNP), nirmatrelvir (PDB: 7SI9), and ensitrelvir (PDB: 7VU6). (C) Dose-response curves of WT, P168S, and ∆P168 Mpro variants using the live-cell Src-Mpro-Tat-fLuc assay with fourfold serial dilution of inhibitor beginning at 10 μM for nirmatrelvir and ensitrelvir or 100 μM for boceprevir (data are means ± SD of biologically independent triplicate experiments). (D) Relative luminescence of cells expressing Src-Mpro-Tat-fLuc variants in the absence of inhibitor. (E) Dose-response curves of nirmatrelvir and ensitrelvir against WT and ∆P168 Mpro in an orthologous VSV-based Mpro cis-cleavage assay (data are means ± SD of biologically independent triplicate experiments).