Identification of Plasmodium falciparum specific translation inhibitors from the MMV Malaria Box using a high throughput in vitro translation screenVida Ahyong, Christine M. Sheridan, Kristoffer E. Leon, Jessica N. Witchley, Jonathan Diep, and Joseph L. DeRisi
Malaria Journal, 2016Abstract: Background: A major goal in the search for new anti-malarial compounds is to identify new mechanisms of action
or new molecular targets. While cell-based, growth inhibition-based screening have enjoyed tremendous success, an
alternative approach is to specifically assay a given pathway or essential cellular process.
Methods: Here, this work describes the development of a plate-based, in vitro luciferase assay to probe for inhibitors
specific to protein synthesis in Plasmodium falciparum through the use of an in vitro translation system derived from
the parasite.
Results: Using the Medicines for Malaria Venture’s Malaria Box as a pilot, 400 bioactive compounds with minimal
human cytotoxicity profiles were screened, identifying eight compounds that displayed greater potency against the P.
falciparum translation machinery relative to a mammalian translation system. Dose–response curves were determined
in both translation systems to further characterize the top hit compound (MMV008270).
Conclusions: This assay will be useful not only in future anti-malarial screening efforts but also in the investigation of
P. falciparum protein synthesis and essential processes in P. falciparum biology.
