2. Academic Validation
  3. ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments

ABMA, a small molecule that inhibits intracellular toxins and pathogens by interfering with late endosomal compartments

  • Sci Rep. 2017 Nov 14;7(1):15567. doi: 10.1038/s41598-017-15466-7.
Yu Wu 1,  Valérie Pons 2,  Amélie Goudet 1,  Laetitia Panigai 3,  Annette Fischer 4,  Jo-Ana Herweg 4,  Sabrina Kali 5,  Robert A Davey 6,  Jérôme Laporte 3,  Céline Bouclier 1,  Rahima Yousfi 7,  Céline Aubenque 7,  Goulven Merer 2,  Emilie Gobbo 1,  Roman Lopez 2,  Cynthia Gillet 8,  Sandrine Cojean 9,  Michel R Popoff 10,  Pascal Clayette 7,  Roger Le Grand 11,  Claire Boulogne 8,  Noël Tordo 5,  Emmanuel Lemichez 12,  Philippe M Loiseau 9,  Thomas Rudel 4,  Didier Sauvaire 3,  Jean-Christophe Cintrat 2,  Daniel Gillet 13,  Julien Barbier 14
Affiliations

Affiliations

  • 1 Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), CEA, Université Paris-Saclay, LabEx LERMIT, 91191, Gif-sur-Yvette, France.
  • 2 Service de Chimie Bio-organique et Marquage (SCBM), CEA, Université Paris-Saclay, LabEx LERMIT, 91191, Gif-sur-Yvette, France.
  • 3 Agence Nationale de Sécurité du Médicament et des Produits de santé (ANSM), CTROL/TOMIC, 34740, Vendargues, France.
  • 4 Biocenter, Department of Microbiology, University of Würzburg, 97074, Würzburg, Germany.
  • 5 Antiviral Strategies Unit, Virology Department, Institut Pasteur, 75015, Paris, France.
  • 6 Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, 78227, TX, USA.
  • 7 ImmunoPharmacology and Biosafety Laboratory, BERTIN Pharma, CEA, 92260, Fontenay-aux-Roses, France.
  • 8 IMAGERIE GIF, Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris-Sud, Université Paris-Saclay, 91190, Gif-sur-Yvette, France.
  • 9 Antiparasitic Chemotherapy, Faculty of Pharmacy, BioCIS, UMR 8076 CNRS, University Paris-Sud, 92296, Chatenay-Malabry, France.
  • 10 Bactéries anaérobies et Toxines, Institut Pasteur, 75015, Paris, France.
  • 11 U1184, Immunology of Viral Infections and Autoimmune Diseases, IMETI, IDMIT, CEA, 92260, Fontenay-aux-Roses, France.
  • 12 INSERM U1065, Equipe Labellisée Ligue Contre le Cancer, Centre Méditerranéen de Médecine Moléculaire (C3M), Université de Nice Sophia-Antipolis, 06204, Nice, France.
  • 13 Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), CEA, Université Paris-Saclay, LabEx LERMIT, 91191, Gif-sur-Yvette, France. daniel.gillet@cea.fr.
  • 14 Service d'Ingénierie Moléculaire des Protéines (SIMOPRO), CEA, Université Paris-Saclay, LabEx LERMIT, 91191, Gif-sur-Yvette, France. julien.barbier@cea.fr.
PMID: 29138439 DOI: 10.1038/s41598-017-15466-7
Abstract

Intracellular pathogenic Microorganisms and toxins exploit host cell mechanisms to enter, exert their deleterious effects as well as hijack host nutrition for their development. A potential approach to treat multiple pathogen infections and 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 screening for its capacity to protect human cells and mice against ricin toxin without toxicity. This compound efficiently protects cells against various toxins and pathogens including viruses, intracellular bacteria and Parasite. ABMA provokes Rab7-positive late endosomal compartment 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-endosomal compartments, 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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