Fig. 2: Polymerization modes of SARS-CoV nsp12 and incorporation of nucleotide analogues.

a, Steady-state data showing extension of hairpin and primer-template RNA substrates by the nsp12:7L8:8 complex. Graphs show the fraction of primer, intermediate and full-length products over time. Additional extension products beyond the full-length observed on the PT substrate are attributed to nsp8 RNA 3’-terminal adenylyltransferase activity⁴⁰. b,c, Incorporation of nucleoside analogues T-705 and T1105 with different RNA substrates in the absence of GTP or ATP. Red dots show analogue incorporation sites at the omitted nucleotide positions. Incorporation of correct nucleotides shown in green and mismatches in red. c, Left panel shows products obtained with 100 μM each analogue after 5 minutes. Right panel shows time-course in the presence of 10 μM of each analogue and absence of GTP. Only partial site assignments were possible with the hairpin substrate due to drastic differences in RNA migration attributed to changes in residual RNA structure following analogue incorporation.