Fig. 4: Structural complexity in SARS-CoV-2 −1 PRF.
a,b, After the ribosome unfolds upstream genomic structures, the FSE refolds, resulting in a 3D fold in which the 5′ end is either threaded through a ring in the FSE pseudoknot (inset, hole indicated in yellow), as captured in our cryo-EM structure (a) or left unthreaded (b). The model in b reflects an alternate fold with the same pseudoknotted secondary structure but distinct tertiary arrangement, as captured by de novo modeling. The torsional restraint model suggests that the cryo-EM-resolved conformation in a promotes pausing at the slippery site and ribosomal frameshifting and should be targeted for destabilization relative to alternate folds (b) in antiviral efforts seeking to disrupt frameshifting. c, The phyloP score from 119 diverse coronaviruses superimposed over a 3D model of the SARS-CoV-2 FSE, where coloring is centered over the average phyloP score of the entire viral genome (other comparisons are provided in Supplementary Fig. 6).
