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Development of a semi-automated image-based high-throughput drug screening system
Remzi Onur Eren1, Dmitry Kopelyanskiy1, Dimitri Moreau2
1Department of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland.
Frontiers in Bioscience (Elite Edition)
|September 21, 2017
Summary
Leishmania RNA virus 1 (LRV1) worsens leishmaniasis. A new high-throughput drug screen identified 14 compounds to reduce parasite growth, aiding drug discovery for Leishmania infections.
Area of Science:
- Parasitology
- Virology
- Immunology
Background:
- Leishmania RNA virus 1 (LRV1) exacerbates Leishmania pathogenesis.
- LRV1 presence correlates with treatment failure in Leishmania infections.
- Toll-like receptor 3 (TLR3) mediates innate sensing of LRV1.
Purpose of the Study:
- To establish a high-throughput drug screening (HTDS) protocol for identifying parasiticidal compounds.
- To screen the Prestwick chemical library against Leishmania (Viannia) guyanensis infected macrophages.
- To assess drug toxicity on host cells concurrently.
Main Methods:
- Developed a semi-automated, image-based HTDS protocol.
- Utilized primary murine macrophages infected with LRV1-containing L. guyanensis.
- Performed two independent screens using the Prestwick chemical library.
Main Results:
- Identified 14 hit compounds demonstrating significant parasiticidal activity.
- Achieved over 69% reduction in parasite growth compared to controls.
- The HTDS protocol allowed simultaneous evaluation of host cell toxicity.
Conclusions:
- The developed HTDS protocol is effective for discovering anti-Leishmania drugs.
- Drug repurposing efforts against Leishmania can be accelerated using this method.
- This approach facilitates the identification of compounds with both efficacy and safety.
