A research team has computationally designed a synthetic peptide that enables modular detection of the enzymatic activity of coronavirus 3C-like protease (3CLPro), an enzyme essential for viral replication and maturation. When incorporated into bioluminescent or fluorescent reporter proteins, the optimized peptide produced clear loss-of-signal or gain-of-signal responses corresponding to different 3CLPro expression levels. Unlike conventional tests that primarily indicate whether viral molecules are present, this proof-of-concept strategy measures protease activity, which may more closely reflect functional viral processes.