Computational similarity screening discovered 21 analogs from these hits. Among them, the two best compounds 147 and 148 display IC50 values of 0.3 and 3 µM, respectively. A variety of SARS‐CoV‐1 Mpro inhibitors have been identified through virtual screening (VS) as an alternative to HTS. VS of 50 240 structurally diverse small molecules allowed to identify 104 molecules with anti‐SARS‐CoV‐1 activity. Compound 149 (Figure 34) demonstrated potent enzyme inhibition (IC50, 2.5 μM) and an EC50 of 7 μM in Vero cell‐based SARS‐CoV‐1 plaque reduction assays