Polyanion delivery and protection systems against viral infections – TerminAnion

Current outbreak of SARS-CoV-2 virus and its social, health and economic impact put forward the need for i) potentially generic protection system that can be applied to both surfaces and persons to limit/eliminate transmission during the exponential phase of the outbreaks; ii) development of predictive models that can match the structural properties of a given virus with a family of potentially antiviral component.
In this project, we aim to produce molecular weight controlled polyanionic structures obtained via controlled degradation of naturally occurring polyanionic polysaccharides and to determine the optimal chain length for antiviral activity against SARS-CoV-2 virus. The interaction between the ACE2 receptors from host cells and the spike proteins of the SARS-CoV-2 is a potential target for such physical interruption for the viral infection process. Thus, a family of polyanions will be developed to be able to interact with spike glycoproteins from SARS-Cov-2. SARS-CoV-2 pseudoparticles (pp) encoding GFP or luciferase reporter gene are already available in partners lab for the screening of the polyanions. Then SARS-COV-2 pp will be used to infect HEK293 cells. The polyanions will also be used as an antiviral agent in the form of thin films, hydrogels or nanoparticles by using supramolecular assemblies with a polycation, such as polyarginine. First data obtained will allow to develop a mathematical model considering the viral structures and the corresponding polyanion structures to be able to predict and produce preventive measures for the current and future emerging viral outbreaks.
Finally, our project will address three of the thematic declared as priorities for OMS: i) infection prevention and control measures in the healthcare setting and in community settings; ii) therapeutic targets and assessment models for drug candidates and iii) Predictive and retrospective digital models.
Our consortium is very strong and highly multidisciplinary, it mixes fundamental and applied research in the field of biopolymers, surface coatings, virology, data sciences and artificial intelligence. It is based on 2 academic partners, Inserm Unit 1121 “Biomaterials and Bioenginering” and Inserm Unit 1110 “Institute of viral and liver diseases” and 2 companies, SPARTHA Medical and PRESTE (as subcontractor).
Our project aims to i) use knowledge from Partners (Inserm U1121/SPARTHA Medical) to optimize polyanionic molecule able to show antiviral properties against SAR-CoV-2 (Inserm U1110); ii) use a stabilization agent (such as polycation based on supramolecular assemblies) (SPARTHA Medical) that will improve polyanion efficacy and will allow to produce viral barriers in the form of films, hydrogels or nanoparticles; iii) harness the recent availability of the tools in big data research, machine learning and conventional optimization techniques, to create first empirical models predicting the polyanion properties versus the infection virus particle properties. This will enable to match the correct chemistry with a given virus for future fast response preventive solutions (PRESTE) and to be ready for the next viruses as this is a general strategy. Each partner will rely on its already mature skills useful to the TerminAnion project which will guarantees a fast start of the project with first significative results from month 6.
Four main impacts of the project are foreseen: i) a system that can be modified for future viral outbreaks according to the surface structure of the virus; ii) Different modes of application (spray for medical surfaces, self-standing films for nasal protection, hydrogels for oral protection, nanoparticles for systemic application); iii) Potential high-throughput production and discovery of future antiviral agents with a degradation based methodology; iv) Matching of antiviral infection activities together with the protection against cytokine storm.