Identification of SARS-CoV-2 RNA ibinding proteins durig viral replication – CoV-2RBP

The beginning of 2020 has seen the emergence of COVID-19 pandemic, a respiratory disease caused by a novel coronavirus (CoV), the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In the absence of efficient cure or vaccine currently available, there is an imminent need to better understand the molecular mechanisms supporting the replication of this new virus and to identify new targets to control its spread.
CoV are positive RNA viruses and protein and viral RNAs interactions are crucial in determining the molecular switches towards progression of infection. However, our comprehension of the protein-viral RNA interaction network occurring during SARS-CoV-2 replication is limited. The present project aims to identify viral and host factors that interact with SARS-CoV-2 RNAs and that impact viral replication in cellular models of infection. For this, we will rely on cellular and molecular approaches to specifically label SARS-CoV-2 RNA during (i) Early stages of infection, from viral entry to transcription replication, (ii) from transcription-replication to viral particles formation, and (iii) in viral particles. Viral RNA-protein complexes will then be cross-linked, isolated and interacting factors will be identified by Mass spectrometry. Proteins of interest will be further validated for their interaction with SARS-CoV-2 RNA and their role in viral replication will be assessed.
The project will gather the laboratory “Génomes, biologie cellulaire et thérapeutique" at hospital Saint Louis, Paris and the “Host-Virus Interactions team” at Institut Cochin, Paris and will benefit from their complementary expertise in cellular and molecular approaches to tackle host-virus interactions. In a year time, this study will not only provide new insights into COVID-19 pathogenesis but will also guide future efforts to exploit host and/or viral factors as therapeutic targets for treating and/or preventing SARS-CoV-2 infection.