Discovery of pseudoknots in the SARS-CoVID-2 RNA genome with SNP analysis

The Bevilacqua lab has contributed to the field of RNA biology through two disparate approaches. One isrigorous ribozyme mechanism and the other is discovery-based RNA structural genomics. A major goal of theparent award is to bridge these two areas to discover new RNA biology and to characterize it at the molecularlevel. This proposal advances ways to investigate RNA structure and its contribution to the COVID-19outbreak. We have already computationally identified structural domains in the RNA genome of SARS-CoV-2,which causes COVID-19, and confirmed these with recent reports on BioRxiv. Uniquely, we identified potentialpseudoknots, which are regions of RNA folding complexity that are typically essential for function. The plan forthe summer is for our undergraduate student Peter Forstmeier to work through the thousands of availableSARS-CoV-2 genomes that contain single nucleotide polymorphisms (SNPs) to identify changes in pseudoknotstrength and RNA folding. SNPs in pseudoknots may lead to changes in the stability of the structure, as so-called riboSNitches. The effect of these SNPs on pseudoknots may have implications on the spread andpotential virulence of COVID-19. Our hypothesis is that such information will provide targets for therapeutics,both antisense oligonucleotides and small molecules, which can halt spread of the virus. This administrativesupplement would provide a unique opportunity for Peter to advance his training to pursue his eventual goal ofbeing a physician-scientist. Because it is computational, it is amenable to working from home during thepandemic, and we can mentor Peter using videoconferencing. Peter is a rising junior and has already spent ayear in the Bevilacqua lab developing his coding skills and preparing a pipeline to search for novel RNAstructures making him a good fit for this project.