Fig. 3: Molecular basis of remdesivir’s incorporation selectivity.
From: Structural basis for substrate selection by the SARS-CoV-2 replicase
a, Chemical structures of ATP and RDV-TP, highlighting the position of the RDV-TP 1′ cyano group. b, Cryo-EM densities of the S2_RDV-TP structure, coloured according to fitted model chains. Zoom-in on the bound RDV-TP illustrates the RDV-TP 1′ cyano group is accommodated in a hydrophilic pocket formed by motif B and C residues. Protein surface is coloured according to electrostatics. c–e, Comparison of the active sites of the S1_RDV-TP (c), S4_GTP (d) and S5_CTP (e) structures reveals that the RdRp cyano pocket can also bind a water molecule (map density around the water shown in mesh), which needs to be displaced for RDV-TP binding. f, A comparison of the S2_RDV-TP and S4_GTP structures reveals two predominant rotamers of R555 that mediate either a pi–pi stacking (red dotted lines) or a H-bond (blue dotted line) interaction with the incoming NTP.
