
@article {85902,
	title = {Disrupting Plasmodium UIS3-host LC3 interaction with a small molecule causes parasite elimination from host cells.},
	journal = {Commun Biol},
	volume = {3},
	year = {2020},
	month = {2020 Nov 19},
	pages = {688},
	abstract = {<p>The malaria parasite Plasmodium obligatorily infects and replicates inside hepatocytes surrounded by a parasitophorous vacuole membrane (PVM), which is decorated by the host-cell derived autophagy protein LC3. We have previously shown that the parasite-derived, PVM-resident protein UIS3 sequesters LC3 to avoid parasite elimination by autophagy from hepatocytes. Here we show that a small molecule capable of disrupting this interaction triggers parasite elimination in a host cell autophagy-dependent manner. Molecular docking analysis of more than 20 million compounds combined with a phenotypic screen identified one molecule, C4 (4-{[4-(4-{5-[3-(trifluoromethyl) phenyl]-1,2,4-oxadiazol-3-yl}benzyl)piperazino]carbonyl}benzonitrile), capable of impairing infection. Using biophysical assays, we established that this impairment is due to the ability of C4 to disrupt UIS3-LC3 interaction, thus inhibiting the parasite{\textquoteright}s ability to evade the host autophagy response. C4 impacts infection in autophagy-sufficient cells without harming the normal autophagy pathway of the host cell. This study, by revealing the disruption of a critical host-parasite interaction without affecting the host{\textquoteright}s normal function, uncovers an efficient anti-malarial strategy to prevent this deadly disease.</p>
},
	issn = {2399-3642},
	doi = {10.1038/s42003-020-01422-1},
	author = {Setua, Sonali and Enguita, Francisco J and Chora, {\^A}ngelo Ferreira and Ranga-Prasad, Harish and Lahree, Aparajita and Marques, Sofia and Sundaramurthy, Varadharajan and Mota, Maria M}
}
