High-Throughput Screening Platform To Identify Inhibitors of Protein Synthesis with Potential for the Treatment of Malaria
Fábio K. Tamaki, Fabio Fisher, Rachel Milne, Fernando Sánchez-Román Terán, Natalie Wiedemar, Karolina Wrobel, Darren Edwards, Hella Baumann, Ian H. Gilbert, Beatriz Baragaña, Jake Baum, Susan Wyllie
Abstract
IVT) to be identified. The primary assay in this platform monitors the translation of a luciferase reporter in a P. falciparum lysate-based expression system. Hits identified in this primary assay are assessed in a counterscreen assay that enables false positives that directly interfere with the luciferase to be triaged. The remaining hit compounds are then assessed in an equivalent human IVT assay. This platform of assays was used to screen MMV's Pandemic and Pathogen Box libraries, identifying several selective inhibitors of protein synthesis. We believe this new high-throughput screening platform has the potential to greatly expedite the discovery of antimalarials that act via this highly desirable mechanism of action.