Related Experiment Video
Updated: Jun 14, 2025
Isolation And Dendritic Cell-Uptake of Small Extracellular Vesicles from Echinococcus granulosus
Published on: March 28, 2025
Repurposing of a library for high-content screening of inhibitors against Echinococcus granulosus
Weinan Zheng1, Gaofei Lv2, Jun Li3
1Department of Disease Biology, Global Health Drug Discovery Institute, Beijing, 100000, China. weinan.zheng@ghddi.org.
Background:
Cystic echinococcosis (CE) is a zoonotic disease caused by the larval stage of the dog tapeworm Echinococcus granulosus sensu lato (E. granulosus), with a worldwide distribution. The current treatment strategy for CE is insufficient. Limited drug screening models severely hamper the discovery of effective anti-echinococcosis drugs.
Methods:
In the present study, using high-content screening technology, we developed a novel high-throughput screening (HTS) assay by counting the ratio of propidium iodide-stained dead protoscoleces (PSCs) to the total number of PSCs. In vitro and ex vivo cyst viability assays were utilized to determine the effect of drugs on cyst viability.
Results:
Using the newly established HTS assay, we screened approximately 12,000 clinical-stage or The Food and Drug Administration (FDA)-approved small molecules from the Repurposing, Focused Rescue, and Accelerated Medchem (ReFRAME) library, as well as the LOPAC1280 and SelleckChem libraries, as a strategic approach to facilitate the drug discovery process. Initial screening yielded 173 compounds with anti-echinococcal properties, 52 of which demonstrated dose-response efficacy against E. granulosus PSCs in vitro. Notably, two agents, omaveloxolone and niclosamide, showed complete inhibition upon further validation in cyst and microcyst viability assays in vitro after incubation for 3 days, and in an ex vivo cyst viability assay using cysts isolated from the livers of mice infected with E. granulosus, as determined by morphological assessment.
Conclusions:
Through the development of a novel HTS assay and by repurposing libraries, we identified omaveloxolone and niclosamide as potent inhibitors against E. granulosus. These compounds show promise as potential anti-echinococcal drugs, and our strategic approach has the potential to promote drug discovery for parasitic infections.
Insights
Researchers developed a new high-throughput screening assay to find drugs for cystic echinococcosis (CE). Omaveloxolone and niclosamide were identified as potent compounds against Echinococcus granulosus, offering hope for new CE treatments.
Area of Science:
- Parasitology
- Drug Discovery
- High-Content Screening
Background:
- Cystic echinococcosis (CE) is a widespread zoonotic disease caused by Echinococcus granulosus.
- Current treatments for CE are insufficient, and effective drug discovery is hindered by limited screening models.
Purpose of the Study:
- To develop a novel high-throughput screening (HTS) assay for identifying anti-echinococcal compounds.
- To screen existing drug libraries for potential CE therapeutics.
- To validate promising drug candidates using in vitro and ex vivo assays.
Main Methods:
- Developed a novel HTS assay using propidium iodide staining to assess Echinococcus granulosus protoscolex viability.
- Screened approximately 12,000 clinical-stage or FDA-approved small molecules from diverse libraries.
- Utilized in vitro and ex vivo cyst viability assays to validate drug efficacy.
Main Results:
- The HTS assay identified 173 compounds with anti-echinococcal activity, with 52 showing dose-response efficacy.
- Omaveloxolone and niclosamide demonstrated complete inhibition of Echinococcus granulosus in vitro and ex vivo assays.
- These compounds were validated using cyst and microcyst viability assays.
Conclusions:
- A novel HTS assay was successfully developed and utilized for drug discovery in cystic echinococcosis.
- Omaveloxolone and niclosamide were identified as potent inhibitors of Echinococcus granulosus.
- This strategic approach shows potential for accelerating the discovery of drugs for parasitic infections like CE.
