Identification of lead compounds targeting the cathepsin B-like enzyme of Eimeria tenella

Cysteine peptidases have been implicated in the development and pathogenesis of Eimeria . We have identified a single-copy cathepsin B-like cysteine peptidase gene in the genome database of Eimeria tenella ( EtCatB ). Molecular modeling of the predicted protein suggested that it differs significantly from host enzymes and could be a good drug target. EtCatB was expressed and secreted as a soluble, active, glycosylated mature enzyme from Pichia pastoris . Biochemical characterization of the recombinant enzyme confirmed that it is cathepsin B-like. Screening of a focused library against the enzyme identified three inhibitors (a nitrile, a thiosemicarbazone, and an oxazolone) that can be used as leads for novel drug discovery against Eimeria . The oxazolone scaffold is a novel cysteine peptidase inhibitor; it may thus find widespread use.