We have recently characterized the interaction between the SUD domain of SARS-CoV-2 Nsp3 and non-canonical nucleic acid structures called G-quadruplexes or G4 (Lavigne et al., 2021, Nucleic Acids Research). Specific molecules known as G4-ligands prevent this interaction and some of them inhibit SARS-CoV-2 infection in A549-Ace2 cells (European patent 20 306 606.3).
Few unstable G4s have been predicted in the SARS-CoV-2 RNA genome, which contrasts with the enrichment of stable and functional G4s in cellular mRNAs (UTRs and introns). In addition, SARS-CoV-2 SUD interacts with the Paip/PABP complex (Lei et al., 2021, Embo Journal) which suggests its role as regulator of cellular translation. These data lead us to hypothesize that SARS-CoV-2 SUD interacts with specific G4s present in cellular mRNAs and modulates their translation, localization of stability. These potential effects could be involved in the viral replication process and/or in the immune and inflammatory cell responses to viral infection.
The aim of this project is to characterize the cellular RNA sequences interacting with SARS-CoV-2 SUD. The identified RNA sequences will be analyzed for different properties such as their (i) enrichment in G4s or other RNA secondary structures (ii) interaction with SUD and (iii) involvement in specific cellular pathways. The identified SUD/RNA complexes will also be studied for their role in SARS-CoV-2 replication or in the cell response to viral infection.
