Isatin compounds as noncovalent SARS coronavirus 3C-like protease inhibitors

A series of isatin derivatives were synthesized and tested against SARS CoV 3C-like protease. Substitutions at the N-1 and C-5 positions were examined to elucidate the differences in substrate binding sites of the rhinovirus 3C protease and SARS CoV 3C-like protease. Compound Sf shows significant inhibition with an IC₅₀ of 0.37 μM. Further study showed that, unlike the irreversible covalent binding of isatin derivatives to human rhinovirus 3C protease, the compounds tested in this study are all noncovalent reversible inhibitors.