Research ArticleInfectious Disease

Metal-captured inhibition of pre-mRNA processing activity by CPSF3 controls Cryptosporidium infection

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Science Translational Medicine  06 Nov 2019:
Vol. 11, Issue 517, eaax7161
DOI: 10.1126/scitranslmed.aax7161

Controlling Cryptosporidium

The apicomplexan parasite Cryptosporidium causes potentially life-threatening gastrointestinal symptoms, and treatment can be ineffective in vulnerable patient groups. Swale et al. show that a benzoxabarole, previously found to be effective against other apicomplexans, controlled cryptosporidiosis better than the standard of care in both neonatal and immunocompromised mouse models of infection. Biochemical assays and a cocrystal structure of the benzoxabarole bound to the active site of parasitic cleavage and polyadenylation specificity factor 3 (CPSF3) suggested that the selective targeting of Cryptosporidium by the benzoxabarole resulted from inhibition of parasitic pre-mRNA processing. This study proposes a potential treatment against cryptosporidiosis and provides insight into how oxabaroles inhibit apicomplexan parasites.

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