Fig. 7: The potential nucleoprotein (NP) binding site on VP35.

a, b Superimposition of the MeV (measles virus) P_XD–N^MoRE complex (PDB: 1T6O) (a) and the NiV (Nipah virus) P_XD–N^MoRE complex (PDB: 7PNO) (b) onto the mVP35 IID of MARV polymerase complex. c Superimposition of VP35 IIDs from MARV and EBOV polymerases determined in this study. Key residues reported for NP–VP35 IID interactions are shown as sticks and colored by cyan (mVP35) and magenta (eVP35), respectively. The P_XD and N^MoRE of MeV are colored in limon and purple, respectively and the P_XD and N^MoRE of NiV are shown in lime green and dark blue, respectively. mVP35d IID is shown in orange and eVP35d IID in blue-white. d The proposed model for RNA synthesis by filovirus polymerases. Briefly, in the apo state without RNA binding (I), the priming loop of the filovirus polymerase is ordered or partially ordered, while the instruction loop is retained in the PRNTase domain. In the pre-initiation state once the replication promoter is bound to the polymerase (II), the recognition of the promoter RNA does not seem to affect the conformation of the priming loop and the instruction loop in filoviruses. In the initiation state (III), the priming loop inserts into the catalytic cavity, and an aromatic or ring-based residue from the loop may participate in the stabilization of the first two nucleotide to facilitate the formation of the first phosphodiester bond^11,65. With the incorporation of more NTPs into the nascent RNA, the RNA product grows longer, and the polymerase gradually enters an elongation state (IV), in which both the priming loop and the instruction loop are retracted into the PRNTase domain or even completely disordered, allowing the RNA product to pass through the product exit channel.