Fig. 5. Mechanism of suramin inhibition of EBOV L–VP35.
a, Suramin inhibits the replication activity of the EBOV L–VP35 complex in an enzymatic assay, with an IC50 value of 11.16 µM. b, Suramin inhibits EBOV RNP activity in EBOv-GLuc-Hyg replicon cells with an EC50 value of 0.4 µM. Data in a,b are mean ± s.d. of three or four independent experiments. c, Overall structure of the L–VP35–suramin complex. The L–VP35 complex is shown in cartoon representation with the same colours as in Fig. 4. Suramin is shown as a stick model in purple with a dashed outline. Top left, close-up view of the suramin-binding site in surface representation, showing that suramin is located in the NTP entry channel. d–f, Atomic interactions between suramin and EBOV L. Key residues that are responsible for suramin binding are shown as sticks and coloured according to subdomain. Hydrogen bonds and salt bridges are shown as yellow and green dashed lines, respectively.