Towards understanding of immunostimulatory properties of SARS-CoV-2 RNAs

About Summary COVID-19 represents a massive health threat for humans and has already caused huge economic problems all over the world. Profound knowledge of SARS-CoV-2 interaction with the host and the host immune response are needed to control this virus and to readjust antiviral therapy currently used to treat COVID-19. The first line of defense against viral infections is antiviral innate immunity. The host pattern recognition receptors (PRRs) detect specific molecular patterns exclusively found in pathogens and initiate the adequate immune response. Among them, the RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) and zinc finger antiviral proteins (ZAP) are ubiquitously expressed RNA binding proteins that detect viral RNA in the cytosol to initiate innate antiviral responses and restrict viral replication. The main objective of SARS-Cov-2immunRNAs is to bring immunostimulatory SARS-CoV-2 RNAs and their detection by PRRs into the spotlight as an important component of the innate immune response to the virus that predetermines the outcome of viral infection. For this we will: i) determine specific RNA signatures of SARS-CoV-2 on PRRs, such as RIG-I, MDA5, LGP2 and ZAP; ii) obtain a comparative view on dinucleotide biases, primary/secondary and ternary structures for PRR-specific biological SARS-CoV-2 RNA ligands; iii) validate and compare immunostimulatory properties (adequate or detrimental) of novel PRR-specific SARS-CoV-2 RNA ligands. Our hypothesis is that detrimental activation of PRRs by immunostimulatory SARS-CoV-2 RNA ligands could explain an early robust host immune response underlying the severity of pneumonia and the infection outcome of COVID-19. In-depth knowledge of SARS-CoV-2 RNA immunostimulatory potential will help in understanding of how to induce protective innate antiviral immune responses to this virus and to interfere with detrimental innate immune responses. Additionally, SARS-CoV-2 immunostimulatory viral ligands will also provide new potential adjuvants for vaccines or components of prophylactic vaccines. Collaboration Andrea Di Gioacchino and Simona Cocco from Physics Laboratory of the Ecole Normale Supérieure, PSL & CNRS UMR8063, Sorbonne University, University of Paris Funding SARS-Cov-2 immunRNAs - AAP FLASH COVID-1 CoV-2Sensing - Institut Pasteur call for projects