Trypanosomatids are protozoan parasites that cause human and animal neglected diseases. Despite global efforts, effective treatments are still much needed. Phenotypic screens have provided several chemical leads for drug discovery, but the mechanism of action for many of these chemicals is currently unknown. Recently, chemogenomic screens assessing the susceptibility or resistance of parasites carrying genome-wide modifications started to define the mechanism of action of drugs at large scale. In this review, we discuss how genomics is being used for drug discovery in trypanosomatids, how integration of chemical and genomics data from these and other organisms has guided prioritisations of candidate therapeutic targets and additional chemical starting points, and how these data can fuel the expansion of drug discovery pipelines into the era of artificial intelligence.
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Cover Image
Macrophages are innate immune cells responsible for a variety of tissue-specific homeostatic functions and responding to infiltrating pathogens. A lot of what we know about macrophages comes from studies on unphysiological 2D plastic dishes, however new insights into macrophage biology are emerging thanks to 3D cell culture technology (see the review in this issue by Cutter et al., pages 387–401). Depicted here is a macrophage suspended within a neon 3D dimension. Image provided by Katrina Binger.
Targeting trypanosomes: how chemogenomics and artificial intelligence can guide drug discovery
Lionel Urán Landaburu, Mercedes Didier Garnham, Fernán Agüero; Targeting trypanosomes: how chemogenomics and artificial intelligence can guide drug discovery. Biochem Soc Trans 27 February 2023; 51 (1): 195–206. doi: https://doi.org/10.1042/BST20220618
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