Figure 6.

Model comparing ss- and dsRNA cleavage by Nsp15. Nsp15 cleaves ssRNA mainly through engagement of the U in the active site, with limited binding by upstream or downstream nucleotides. ssRNA is readily accessible to the Nsp15 active site. Nsp15 cleaves dsRNA by multiple interaction sites, spanning three protomers and both trimers that compose the hexamer. The U base must flip out of the base-paired helix to be cleaved; distortion in the RNA is stabilized through π-stacking with W333. Figure made in Biorender.