Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Anna Marie Pyle (anna.pyle@yale.edu).

No unique reagents were generated in this study.

All ShapeMapper outputs, secondary structure files, and multiple sequence alignments used in this work are available at the GitHub repository: https://github.com/pylelab/SARS-CoV-2_SHAPE_MaP_structure. SHAPE-MaP data has been deposited on the Gene Expression Omnibus (GEO) database under the accession GSE154171.

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