Shotgun proteomics of SARS-CoV-2 infected cells and its application to the optimisation of whole viral particle antigen production for vaccines

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Grenga, Lucia | Gallais, Fabrice | Pible, Olivier | Gaillard, Jean-Charles | Gouveia, Duarte | Batina, Hélène | Bazaline, Niza | Ruat, Sylvie | Culotta, Karen | Miotello, Guylaine | Debroas, Stéphanie | Roncato, Marie-Anne | Steinmetz, Gérard | Foissard, Charlotte | Desplan, Anne | Alpha-Bazin, Béatrice | Almunia, Christine | Gas, Fabienne | Bellanger, Laurent | Armengaud, Jean

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Abstract Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread quickly around the globe. Currently, no effective vaccine is available to prevent COVID-19 and an intense global development activity is in progress. In this context, the different technology platforms face several challenges resulting from the involvement of a new virus still not fully characterised. Finding of the right conditions for virus amplification for the development of vaccines based on inactivated or attenuated whole viral particles is among them. Here, we describe the establishment of a workflow based on shotgun tandem mass spectrometry data to guide the optimisation of the conditions for viral amplification. In parallel, we analysed the dynamic of the host cell proteome following SARS-CoV-2 infection providing a global overview of biological processes modulated by the virus and that could be further explored to identify drug targets to address the pandemic.

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