Related Experiment Video
Updated: Jun 21, 2026
High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
Published on: October 30, 2021
Discovery of novel antischistosomal scaffolds from the open access Pandemic Response Box
Stefan Biendl1,2, Cécile Häberli1,2, Jennifer Keiser1,2
1Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Background:
Treatment and control of schistosomiasis rely on a single drug, praziquantel. New orally active antischistosomals featuring novel molecular scaffolds are urgently needed to prevent the emergence of resistance.
Methods:
We screened 400 drug-like compounds contained in the open-access Pandemic Response Box (PRB) against newly transformed schistosomula (NTS) at a concentration of 10 µM scoring death, changes in motility, and morphological alterations. Compounds displaying an activity ≥66% at 72 h underwent testing against adult Schistosoma mansoni in vitro. Fast-acting (≥66% at 24 h), nontoxic drugs focusing on late-stage and approved drugs were investigated in the patent S. mansoni mouse model.
Results:
We identified 26 hits active against NTS, of which 17 elicited ≥66% activity against adult S. mansoni following 24 h of drug exposure. The highest activity against adult S. mansoni was observed with MMV1581558 (EC50 value of 0.18 ± 0.01 µM) and nitazoxanide (0.47 ± 0.07 µM). Of the five compounds tested in vivo, MMV1581558 and the approved drug ozanimod reduced average worm burden versus controls by 42 % and 36 %, respectively, after a single oral dose of 200 mg/kg bodyweight in mice harboring a chronic S. mansoni infection.
Conclusion:
MMV1581558 discovered from screening the PRB represents a novel antischistosomal scaffold with high in vitro antischistosomal activity amenable to chemical modification for drug development.
