The authors increase the antiviral activity of 13b against beta coronaviruses of clade b by sacrificing the broad-spectrum nature of 13a through replacing the P2 cyclohexyl moiety in 13a with a small cyclopropyl in 13b. The authors determined the X-ray structure of α-ketoamide 13b and SARS-CoV-2 Mpro complex at 1.95 and 2.20 Å resolution. In one of the structures, the authors found that the key residue, Glu166, forms inactive conformation in protomer B while the 13b compound is bound in the same fashion as in molecule A. Authors also found that the inhibitor binds to the shallow substrate-binding site at the surface of protomers between domains I and II in the inhibited SARS-CoV-2 Mpro.