RAPID: Measuring RNA Tertiary Contacts in SARS-CoV2

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The genome of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes coronavirus disease 2019 (COVID-19) is encoded in RNA. This award funds studies by Dr. Victoria J. DeRose at the University of Oregon in Eugene, OR to characterize the three-dimensional structure of the viral RNA. Dr. DeRose uses platinum compounds that chemically attach to RNA bases to determine distances separating different parts of the RNA. Combining the distance information with computer predictions leads to a picture of the SARS-CoV-2 RNA genome. The impact of the project on society is to identify potential target sites in the viral genome, which provides further leads for the development of therapeutic interventions against the COVID-19 pandemic.Results from this project may impact the ability to understand and develop therapeutics targeting SARS-CoV2 by providing information required to accurately model its RNA structures. Methods developed in this project may be applicable to the next emergent virus. Importantly, this project will support PhD students in research that applies chemical biology to fundamental science with immediate application to a major global crisis.The goal of this project is to enable three-dimensional modeling of SARS-CoV2 RNA structures by measuring tertiary contacts through chemical crosslinking. Platinum (II) crosslinking reagents are used to obtain a library of RNA-RNA interactions in and between SARS-CoV2 RNA domains. The resulting long-range connectivity maps provide distance constraints to complement computational and NMR spectroscopic studies for the derivation of three-dimensional models of the viral RNAs. These models are compared to the RNA in solution and in mammalian cells, helping to expedite small molecule targeting of RNA processes that are critical to virus function.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.