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Toxoplasmosis constitutes a challenge for public health, animal production, and welfare. So far, only a limited panel of drugs has been marketed for clinical applications. In addition to classical screening, the investigation of unique targets of the parasite may lead to the identification of novel drugs. Herein, the authors describe the methodology to identify novel drug targets in Toxoplasma gondii and review the literature with a focus on the last two decades. Over the last two decades, the investigation of essential proteins of T. gondii as potential drug targets has fostered the hope of identifying novel compounds for the treatment of toxoplasmosis. Despite good efficacies in vitro, only a few classes of these compounds are effective in suitable rodent models, and none has cleared the hurdle to applications in humans. This shows that target-based drug discovery is in no way better than classical screening approaches. In both cases, off-target effects and adverse side effects in the hosts must be considered. Proteomics-driven analyses of parasite- and host-derived proteins that physically bind drug candidates may constitute a suitable tool to characterize drug targets, irrespectively of the drug discovery methods.

Toxoplasma gondii infection: novel emerging therapeutic targets