Fig. 6: Druggability and genetic variability of the nucleotide and 5′-RNA sites.
From: Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase
a The nucleotide binding pocket (blue) occupied by AMP-PNP and a cavity (red) that is partially occupied by the 5′-end of the substrate RNA in the transcription complex structure (PDB 7CXM) were identified as druggable sites in our crystal structures. Druggability scores (Dscores) calculated with SiteMap33 are indicated (insets). The location of each binding site in the context of the transcription complex structure is also shown (insets). b Conservation of sidechains lining the AMP-PNP-bound site (left) and the fragment-bound 5′-RNA site (right) is shown across 27 α- and β-coronavirus sequences reviewed in the Uniprot database. Conserved (cyan) and non-conserved (mustard) sidechains are mapped on 3D structures. Asterisks indicate sidechains that are in direct contact with the fragment in structure 5RMM. Residue numbering in SARS-CoV-2 is shown at the top. Viruses associated with human epidemics are highlighted in bold.
