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Scientific result | Virus | Infectious diseases
Two Research Teams from SIMOPRO and SCBM, in collaboration with Texas Biomedical Research Institute and Jilin University, showed that anti-ricin compounds Retro-2, discovered at CEA during researches against bioterrorism, inhibit two families of viruses important for public health (Ebola and Marburg filovirus and enterovirus EV71). These results broaden the antiviral spectrum of Retro-2 type compounds.
Members of the family Filoviridae cause severe, often fatal disease in humans, for which there are no approved vaccines and only a few experimental drugs tested in animal models. Retro-2, a small molecule that inhibits retrograde trafficking of bacterial and plant toxins inside host cells, has been demonstrated to be effective against a range of bacterial and virus pathogens, both in vitro and in animal models. Here, we demonstrated that Retro-2 and its derivatives, Retro-2.1 and compound 25, blocked infection by Ebola virus and Marburg virus in vitro. We show that the derivatives were more potent inhibitors of infection as compared to the parent compound. Pseudotyped virus assays indicated that the compounds affected virus entry into cells while virus particle localization to Niemann-Pick C1-positive compartments showed that they acted at a late step in virus entry. Our work demonstrates a potential for Retro-type drugs to be developed into anti-filoviral therapeutics.Read the French version.
Shtanko O, Sakurai Y, Reyes AN, Noël R, Cintrat JC, Gillet D, Barbier J. Davey RA. Retro-2 and its dihydroquinazolinone derivatives inhibit filovirus infection (2018) Antiviral Research 149, 154-163 http://dx.doi.org/10.1016/j.antiviral.2017.11.016
Dai W, Wu Y, Bi J, Lu X, Hou A, Zhou Y, Sun B, Kong W, Barbier J, Cintrat JC, Gao F, Gillet D, Su W, Jiang C. Antiviral effects of Retro-2cycl and Retro-2.1 against Enterovirus 71 in vitro and in vivo. (2017) Antiviral Research 144, 311-321http://dx.doi.org/10.1016/j.antiviral.2017.07.001
CEA is a French government-funded technological research organisation in four main areas: low-carbon energies, defense and security, information technologies and health technologies. A prominent player in the European Research Area, it is involved in setting up collaborative projects with many partners around the world.