FIGURE 5 | NS5B RNA replicase inhibitors: part 2.

a | X-ray crystallographic structure of the NS5B RNA replicase. The thumb, palm and finger domains are coloured in blue, green and red, respectively. The two catalytic aspartates (residues 318 and 319) are shown in stick and ball style in the active site. Residues that are responsible for resistance to the various inhibitors are coloured according to the resistance pattern: magenta (benzimidazoles/indoles), light blue (thiophenes), brown (benzothiadiazines), yellow (dihydroxypyrimidines) and orange (2'-C-Me nucleosides)⁶³. Figure reproduced with permission from Ref. 63 © (2005) International Medical Press. b | Binding sites for non-nucleoside RNA replicase inhibitors (NNRRIs) at the NS5B polymerase. Whereas there is only one binding site (S282) for the nucleoside reverse replicase inhibitors (NRRIs), there are at least four binding sites for the NNRRIs (NNI sites 1, 2, 3 and 4 for benzimidazole, thiophene carboxylic acid, benzothiadiazine and benzofuran, respectively)^{147, 148, 149} (and A. Y. M. Howe, personal communication). Yellow spheres represent amino acid residues at the NNRRI binding sites; turquoise dots represent Mg²⁺ ions at the catalytic aspartates. Figure is courtesy of Inge Vliegen and Weidong Zhong. c | Structures of NNRRIs.

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