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Human rhinovirus (HRV) 3C protease was inactivated by a series of S-nitrosothiols. These compounds exhibited different inhibitory activities in a time- and concentration-dependent manner with second-order rate constants (k inact /K I ) ranging from 131 to 5360M -1 min -1 . The inactive enzyme could be re-activated by DTT, GSH and ascorbate, which indicated the inactivation mechanism was through an S-transnitrosylation process.