ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments
2017
Intracellular pathogenic microorganisms and toxins exploit host
cell mechanismsto enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat
multiplepathogen
infectionsand that should not induce drug resistance is the use of small molecules that target host components. We identified the compound 1-adamantyl (5-bromo-2-methoxybenzyl) amine (ABMA) from a cell-based
high throughput screeningfor its capacity to protect human cells and mice against
ricin toxinwithout toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and parasite. ABMA provokes Rab7-positive late
endosomalcompartment accumulation in mammalian cells without affecting other organelles (
early endosomes, lysosomes, the
Golgi apparatus, the endoplasmic reticulum or the nucleus). As the mechanism of action of ABMA is restricted to host-
endosomalcompartments, it reduces cell infection by pathogens that depend on this pathway to invade cells. ABMA may represent a novel class of broad-spectrum compounds with therapeutic potential against diverse severe infectious diseases.
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