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Recently, a benzo-1,2,4-thiadiazine was shown to be a potent, specific inhibitor of the hepatitis C virus (HCV) RNA polymerase [J. Biol. Chem. 277 (2002) 32327]. Herein, we present several lines of evidence to demonstrate that thiadiazine compound 4 (C21H21N3O4S) is highly synergistic with interferon-α (IFN-α) and disrupts HCV replicon RNA synthesis with a distinct kinetic profile. A time course analysis...