Fig. 4

Structures of SARS-CoV-2 replication and transcription complex (RTC). A A composite structure of RTC from three PDB coordinates, 7CXM (architecture of nsp7, nsp8 X2, nsp12 and nsp13 X2 bound to RNA template and primer), 6XEZ (the ADP·AlF3, bound in the nsp13 helicase active site), and 7CYQ (nsp9 associated with nsp12 and GDP in the active site of RNA capping). The RNA template pieces bound to nsp13 and nsp12 are not connected and would be pulled by the two enzymes in opposite directions as indicated by the yellow double arrowheads. B, C Zoom-in views of RTC bound to inhibitors, Favipiravir (PDB: 7AAP), Remedisivir (RMP) (PDB: 7B3B), and Suramin (PDB: 7D4F). RdRP (nsp12) is shown in grey in B, C, the three inhibitors are in distinct colors. With several SO₄ groups mimicking the phosphate backbone of RNA, two Sumarin molecules (cyan) compete for the RNA template and primer binding. Remedisivir (blue) is already incorporated in the RNA primer strand at − 3 position. Favipiravir RTD (magenta) occupies the incoming nucleotide position, but the phosphates are in a non-productive conformation. The active site residues are shown in pink-red sticks and Mg²⁺ ions are shown as green spheres