Identification of Lead Compounds Targeting the Cathepsin B-Like Enzyme of Eimeria tenella

Abstract

ABSTRACTCysteine peptidases have been implicated in the development and pathogenesis ofEimeria. We have identified a single-copy cathepsin B-like cysteine peptidase gene in the genome database ofEimeria 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 fromPichia 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 againstEimeria. The oxazolone scaffold is a novel cysteine peptidase inhibitor; it may thus find widespread use.