Following the SARS outbreak, a CoV-1 3CLpro homology model was published in 2003 with comparisons made to the human rhinovirus (HRV) 3Cpro.28 Although these two proteases share very little sequence conservation, the substrate consensus sequences have a Gln residue in common at P1. Analysis of the HRV 3Cpro crystal structure with 1 (rupintrivir; Figure 2) revealed binding interactions that are like those observed for 1 bound to TGEV 3CLpro, which was used in the construction of their homology model. The authors concluded that Michael acceptor 1 would serve as a starting point to expedite the identification of a potent SARS CoV-1 3CLpro inhibitor.