Screening of a chemogenetic library unveils dual-stage antiplasmodials with low cytotoxicity.

Authors

Laura Torres, Matthew E Fishbaugher, Melanie Lam, Alexander T Chao, Calla Martyn, Luying Pei, Debapriya Sengupta, Maxime Dauphinais, Jonathan E Gable, Srinivasa P S Rao, Steffen Renner, W Armand Guiguemde, Sebastian A Mikolajczak, Anke Harupa, Gabriel Mitchell

Published in

Antimicrobial agents and chemotherapy. Pages e0161325. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

The global effort to eradicate malaria requires the development of drugs with novel mechanisms of action and differentiated pharmacological profiles. Both liver and blood phases of Plasmodium infection are essential for disease progression and transmission, making them primary targets for pharmacological intervention. In this study, we established a dual-luciferase reporter assay to simultaneously assess Plasmodium berghei liver-stage development and host cell viability. Screening a library of bioactive small molecules with annotated human targets revealed several inhibitors with potent liver-stage activity and minimal cytotoxicity. Further profiling against Plasmodium falciparum asexual blood stages identified compounds with dual-stage activity, underscoring their potential utility for development as either prophylactic or therapeutic agents. Knowledge of their human targets will facilitate investigation into host- or parasite-directed antimalarial mechanisms, thereby accelerating both biological insight and rational drug development. Our findings constitute a valuable resource for research on malaria biology and the discovery of next-generation antiplasmodials.

PMID:
42831637
Bibliographic data and abstract were imported from PubMed on 05 Oct 2026.

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