CTSL/CAPN1-IN-2 (Compound 14b) is an orally active inhibitor of both CTSL and CAPN1 , with IC 50 values of 6.88 nM and 347.6 nM, respectively. CTSL/CAPN1-IN-2 possesses anti-inflammatory properties and favorable pharmacokinetic characteristics. CTSL/CAPN1-IN-2 exhibits broad-spectrum antiviral activity against coronaviruses by blocking viral entry.