Delivery of corroles using TMV nanoparticles for the development of new anti-poxvirus agents

Poxviruses are double-stranded DNA viruses that infect a wide variety of animals, including humans. If vaccine solutions are available, there is to date practically no specific therapeutic antiviral molecule for poxviruses. We are particularly interested in the Mpox (formerly "monkeypox") which is an infectious disease caused by an orthopox virus, characterized in particular by a rash. At the beginning of May 2022, cases of Mpox not directly linked to travel to Central or West Africa, where the virus is present, were reported in Europe and around the world. Since then, the disease, which can be considered as sexually transmitted disease, has been the subject of reinforced surveillance in France and Europe. We had previously shown that nitrocorroles could be used as a powerful anti-hCMV agent without acute toxicity in mice. We have generated original substituted nitro- and fluoro-corroles and we have discovered that these compounds have good efficacy on poxvirus with broad-spectrum antiviral activity. We now wish to focus on a new approach in nanomedicine for the administration of the corrole derivatives in order to increase efficacy while maintaining safety. To achieve this objective, we propose to use the Tobacco mosaic virus (TMV), as a nanovector. This plant virus shows lack of pathogenicity in humans and has already been successfully applied as drug delivery systems. For this, we plan to add corroles by encapsulation but also by chemical bonds inside or outside the TMV capsid. The antiviral efficacy of the modified TMV nanoparticles will be evaluated by NeoVirTech company in Toulouse (https://neovirtech.com).