Clinical proteomic characterization of the SARS-CoV-2 Spike protein to optimize its detection and the development of serological assays – proteoCOVID

Following the emergence and global spread of a new coronavirus called SARS-CoV-2, there is an urgent need to explore various aspects of this new disease, including its mode of transmission, virus-host interactions and immune response, diagnosis and therapy. This collaborative project leverages the complementary expertise of recognized teams and an industrial partner, all of whom share relevant resources and technologies, including: in vitro production of CoV-2-SARS and related viruses, patient blood samples, recombinant protein production, antibody production, immunoassay (ELISA) and clinical proteomics. This latter approach is at the heart of our project and the driving force behind its innovative aspect. We will carry out the characterization in clinical proteomics of the SARS-CoV-2 Spike (S) protein, which plays an important role in the entry and pathogenesis of the virus, while carrying antigenic epitopes that could be the basis of targeted therapeutic strategies and serological tests. Our tasks include, using the latest generation of mass spectrometer and quantitative multiplex peptide detection, the complete characterization of the S protein in a top-down approach. This proteomic profile applied to S proteins, recombinants, from pseudovirions produced in vitro and from patients, will make it possible to discover the differences and diversity of the protein between these sources (including cleavages, glycosylation and other post-translational modifications...). The knowledge gained from these studies will help basic and applied research. Finally, it is indeed of the utmost importance to control the spread and finally contain SARS-CoV-2 and set up the rapid identification of infected persons and those who are immune (post-exposure, or vaccination). This requires specific and sensitive SARS-CoV-2 serological tests, the development and optimization of which is the final objective of our project.