Fig. 3: Cryo-EM structure reveals the binding environment of JNJ-8003.
a Cryo-EM map of RSV polymerase complex with JNJ-8003. The RdRp, capping, and JNJ-8003 were colored in slate, green, and yellow, respectively. The EM density map display threshold was adjusted to enhance the visibility of JNJ-8003. b Close view of the priming loops and connecting regions from Apo or JNJ-8003 bound RSV (green) and VSV (cyan). Two additional putative docking sites (Site0 and Site1) were highlighted. The transitions of the priming loop and α54 were indicated using curve arrows. RSV L + P and JNJ-8003 were shown as cartoons, and sticks, respectively. c JNJ-8003 binding pocket. JNJ-8003 and residues within 4 Å were shown in sticks. d Two-dimensional interaction patterns of JNJ-8003 and RSV L were highlighted using dashed lines. One putative water molecule was shown as a red sphere. e The ligand binding pocket from the Apo RSV L. f Structural comparison at ligand binding pocket between JNJ-8003 bound and Apo RSV L. Rotamer transitions on H1338 and F1385 were highlighted using arrows. g Comparison of JNJ-8003 unbound NMR structures (pink and green) and the bound cryo-EM structure in the RSV L + P complex (yellow). Conformational transitions upon binding were highlighted using arrows. h, i Structural comparison at the ligand binding pockets from the Apo HMPV (H), and VSV (I). The side chains of key residues were shown in sticks.
