In summary, we show that the tested 3CLpro inhibitors have anti-coronavirus (SARS-CoV-2 and MERS-CoV) protease and cathepsin B/L activities and inhibitor 11d significantly enhances survival of mice fatally infected with SARS-CoV-2 or MERS-CoV when treatment started 1 day post infection. This evidence concerns the gene CTSB and infection.