BioProject

This work provides the first genome-wide analysis of RNA secondary structure in any coronavirus by defining highly stable RNA structures across the entire genomes of Middle Eastern Respiratory Syndrome virus (MERS), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). More...

This work provides the first genome-wide analysis of RNA secondary structure in any coronavirus by defining highly stable RNA structures across the entire genomes of Middle Eastern Respiratory Syndrome virus (MERS), Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), and Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). The work confirms the small number of previously identified RNA structures and defines multiple novel RNA secondary structures throughout the genomes of all three viruses. The analyses suggest provocative new insights into the role(s) of RNA structure in viral replication and evolution. Importantly, it finds that the SARS-like coronaviruses contain multiple conserved novel RNA structures, even in areas of low sequence conservation, suggesting important functions in coronavirus replication and pathogenesis. It also finds that nucleotide variation between sequenced isolates of SARS-CoV-2 is lower in structured regions, and that highly variable nucleotides in structured regions occur at nucleotides that do not impact highly stable RNA structures, suggesting that SARS-CoV-2 is under selective pressure to maintain these RNA structures. Known RNA secondary structures play critical roles in multiple aspects of coronavirus replication, but the extent and conservation of RNA secondary structure across coronavirus genomes was previously unknown. The results provide the first full genome analysis of RNA structure in any coronavirus, and show that highly stable RNA structures are common, and widely distributed throughout the genome. Identifying the full complement of RNA secondary structures in the MERS, SARS-CoV and SARS-CoV-2 genomes, provides scientists with essential information for determining how RNA structure drives viral pathogenesis. The comparative approach together with the analysis of sequence conservation and nucleotide variability provides a new way to identify functionally important RNA structures, and prioritize future studies. There is an urgent need to develop SARS-CoV-2 vaccines and therapeutics. Targeted disruption of RNA structures conserved in SARS-like coronaviruses could provide a safety feature to prevent vaccine-associated disease, or limit the reversion potential of live attenuated vaccine strains. Several groups are pursuing small molecule or RNA-based approaches to limit SARS-CoV-2 replication and pathogenesis. The results will facilitate these efforts by identifying targets for these therapeutic. The results thus enable multiple approaches to the development of SARS-CoV-2 therapetuics. Less...