In 2018, Groutas et al. 151  disclosed a novel class of dual MERS‐CoV and SARS‐CoV‐1 Mpro inhibitors that contain a P3‐piperidine moiety (58–59; Figure 17). These inhibitors were derived from the dipeptidic‐aldehyde bisulfite adduct 57 (GC376), which was clinically studied as a protease inhibitor for its efficacy against CoVs such as the feline infectious peritonitis virus (FIPV). Compounds 58 and 59 showed potent antiviral activity toward MERS‐CoV in cell‐based bioassays (EC50, 0.5 µM for 58 and 0.8 µM for 59). SAR studies revealed that the piperidine moiety engaged in favorable hydrophobic interactions at the S3 and S4 pockets of the protease.