Comparative efficacy and safety of anti-cryptosporidial agents: an in vitro study on nitazoxanide, halofuginone lactate, KDU731, and paromomycin against Cryptosporidium parvum

• Published in: Frontiers in microbiology Vol. 15; p. 1463457
• Main Authors: Whitta, Saffron T G, Lamont, Bridget, Suwanarusk, Rossarin, Russell, Bruce M, Muhsin-Sharafaldine, Morad-Rémy
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 04.10.2024
• Subjects: anti-parasitics; apicomplexa pathogen; cryptosporidiosis; Cryptosporidium; halofuginone lactate; nitazoxanide; Cryptosporidium; apicomplexa pathogen; halofuginone lactate; lipid kinase inhibitors; nitazoxanide; anti-parasitics; paromomycin; cryptosporidiosis
• ISSN: 1664-302X; 1664-302X
• DOI: 10.3389/fmicb.2024.1463457

This study evaluated the effectiveness of anti-cryptosporidial agents nitazoxanide, halofuginone, the pyrazolopyridine analog KDU731, and paromomycin (PMC) in combating the significant zoonotic pathogen . The study utilized HCT-8 host cells to culture and fluorescent microscopy/quantitative PCR (qPCR) for detecting parasitic growth. The efficacy of the compounds was assessed by calculating their inhibitory concentrations (IC) against the total growth of at 48 h post-infection. The study further investigated the impact of these compounds on early parasitophorous vacuole (PV) formation, merozoite egress, host cell viability, and cell growth cycle. KDU731 displayed the most promising profile, with low nanomolar (102 nM ± 2.28) activity and negligible host cell toxicity. This study offers new insights into the relative efficacy and safety of various anti-cryptosporidial compounds, highlighting their stage-specific effects on and the consequential impacts on host cells. Identifying safe and effective anti-cryptosporidial agents contributes significantly to the One Health approach, which emphasizes the importance of integrated strategies in controlling zoonotic diseases.