Extended Data Fig. 11. The inhibition mechanism of suramin against EBOV L-VP35.
(a) The chemical structure of suramin. Each benzene ring group is labeled by a unique symbol. (b) Inhibitory activity of suramin against EBOV L-VP35 complex was measured at enzymatic level. The RNA products were shown in urea-PAGE, and a series of concentration of suramin were added in the enzyme reaction system. The data shown are representative of three independent experiments using different protein preparations. (c) The 50% cytotoxicity concentration (CC50) of suramin was determined with the stable replicon cell. Each data point indicates the mean value of three independent experiments and the error bars represent standard deviation. (d–e) The structures of EBOV L-VP35 (d) and L-VP35-suramin (e) complex are shown in surface representation, and the NTP entry channel is indicated by a dashed circle. The suramin is stuck in the NTP entry channel to prevent NTP substrates reaching active site of RdRp. (f-g) The suramin could also hinder the activity of RdRp by occupying the spaces for product RNA strand. Cutoff view of the L-VP35-suramin complex overlapped with the modeled RNA (f). The tail part of suramin molecule would clash with nascent RNA product strand (g). The template (golden) and product (black) RNA strands are modeled based on the structure of rotavirus polymerase with in situ elongation conformation (PDB 6OGZ).