Ricin is a plant toxin that could be used for criminal or bioterrorist purposes. As part of the inter-ministerial R&D program against CBRNE risks entrusted by the public authorities to the CEA, two teams of researchers from the Institut Frédéric-Joliot have screened a bank of 16,000 small molecules (ChemBridge™ DIVERSet™) in order to identify active compounds that could be used against ricin. Three molecules capable of protecting cells have been isolated. The first two molecules were examined in previous studies.

The third molecule, named ABMA, has just opened its secrets to researchers. In addition to combating ricin, this molecule could be used in a strategy to fight many bacterial toxins (diphtheria, blackleg, C. difficile ToxB, C. sordellii LT), three viruses (Ebola, rabies and dengue fever), the leishmaniasis parasite, and two intracellular bacteria responsible for pulmonary, ocular and genital infections (Simkania negevensis and Chlamydia trachomatis)!

"We discovered that ABMA disrupts a transport pathway in the cell used by all of these microorganisms", explains Daniel Gillet, a researcher at the Institut Frédéric-Joliot. "This is the pathway for the cell to sort and evacuate elements that it does not need, following the internalization of external elements such as nutrients or toxins, for example. This pathway passes through early endosomes, which enclose the external elements, and late endosomes, which transport the elements destined for degradation. In the presence of the ABMA compound, late endosomes accumulate and their contents do not reach the degradation compartments." The researchers have also shown that the ABMA molecule is capable of protecting mice against a lethal dose of ricin.

Optimized ABMA analogs are already being studied in order to obtain broad-spectrum molecules for anti-infectious therapeutic use.