Resources are lacking in terms of treatment for many toxic viruses and bacteria, which are the cause of recent health crises (Ebola virus, Shiga toxin-producing E. coli, cholera, etc.).
For several years, CEA and the Institut Curie have been working to develop a revolutionary approach to treatment: rather than targeting the pathogens directly, scientists from both organizations are seeking to block the cellular mechanism that they depend on to produce their harmful effects. A few years ago, they developed and synthesized compounds called Retro-2 (CEA-Institut Curie patents) capable of blocking the harmful action of many pathogens.
They demonstrated the in-vitro efficacy of these molecules against 3 toxins, 12 viruses, 3 intracellular bacteria and 2 parasites (Gupta et al., 2017). Efficacy has also been proven in vivo in mice against ricin, enterohemorrhagic E. coli, vaccinia virus (smallpox model), enterovirus 71 (a virus causing severe brain damage in children), cytomegalovirus (causing infections in immunosuppressed individuals) and two species of the leishmaniasis parasite. However, further pre-clinical in-vivo tests were required prior to pharmaceutical formulation to identify the precise cellular mechanism that explains the protective action of Retro-2, which had been poorly understood until now.
In a new study published in Nature Chemical Biology on 17 February 2020, researchers from CEA and the Institut Curie, in collaboration with the Carnegie Mellon Institute in the United States, shed light on this mechanism. They discovered that molecules of the Retro-2 family bind to the cellular protein Sec16A and block its effect. Sec16A controls the circulation in the cell of syntaxin-5, a protein that in turn controls the progression of viruses and toxins.
Having identified the intracellular target of Retro-2, researchers can now look at developing a drug candidate with a broad spectrum of applications.