Extended Data Fig. 1: Selection of a proper warhead at the R position.
(a) Chemical structures and bioactivities of designed compounds 1a-e (racemic mixture). Enzymatic inhibitory activities (IC50) and biophysical activities (thermal shift (∆Tm) values) were measured by the FRET and DSF assays, respectively. Data are shown as mean ± SD, n = 3 biological replicates. (b) Racemic mixture 1a was separated by chiral HPLC to stereoisomers (R)-1a and (S)-1a. (c) The active stereoisomer (R)-1a binding pocket of SARS-CoV Mpro. The molecule (R)-1a and Cys145 are displayed as sticks. The covalent bond (pointed by a red arrow) is formed between Cys145 and the warhead of (R)-1a. Fo - Fc density map (σ = 2.5) is shown in gray. Figure (c) was prepared using PyMOL (https://pymol.org).
