Stabilization of this charged protein–ligand transition state by an “oxyanion hole” present in the active site has been observed with certain inhibitor classes by X-ray crystallography and NMR.21,22 A recent report describes the optimization of a series of peptidomimetics designed with an α-ketoamide warhead, which achieves broad-spectrum inhibition against the Mpro for several coronaviruses and enteroviruses.