Fig. 3.

Comparison of coronavirus nsp12 and arterivirus nsp9, containing the highly conserved NiRAN and RdRp domains. (A) Similarity density plot derived from a multiple sequence alignment including RdRp subunits from all nidovirus lineages. To highlight local deviations from the average, areas displaying conservation above and below the mean similarity are shaded in black and gray, respectively. Conserved sequence motifs of NiRAN (subscript N; see also B) and RdRp (subscript R) are labeled. Domain boundaries used for bioinformatics analyses and uncertainty with respect to the NiRAN/RdRp domain boundary are indicated with vertical and by dashed horizontal lines, respectively. Below each plot, the predicted secondary structure elements are presented in gray for α-helices and black for β-strands. (B) Multiple sequence alignment showing the three conserved motifs of the NiRAN domain from representative species across the Nidovirales order. Conserved residues in this alignment are shown in white font, while partially conserved residues are boxed. The bottom line depicts residues also conserved in the arterivirus EAV, which was used for a first experimental analysis of the NiRAN domain (Lehmann et al., 2015a). Abbreviations not explained in the main text: NHCoV, night-heron coronavirus HKU19 (genus Deltacoronavirus); BToV, bovine torovirus (family Coronaviridae, subfamily Torovirinae, genus Torovirus); WBV, white bream virus (family Coronaviridae, subfamily Torovirinae, genus Bafinivirus); YHV, yellow head virus (family Roniviridae, genus Okavirus); CavV, Cavally virus (family Mesoniviridae, genus Alphamesonivirus).

(A) Modified with permission from Lehmann, K.C., Gulyaeva, A., Zevenhoven-Dobbe, J.C., Janssen, G.M., Ruben, M., Overkleeft, H.S. et al., 2015. Discovery of an essential nucleotidylating activity associated with a newly delineated conserved domain in the RNA polymerase-containing protein of all nidoviruses. Nucleic Acids Res., 43, 8416–8434.