The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection—suramin inhibits EV71 infection in vitro and in vivo

Figures & data

Figure 1 Suramin was identified as an EV71 inhibitor. (A) Suramin inhibits the replication of EV71 isolates Fuyang573, SH12-036, SH12-276 and SEP-4, without cytotoxicity. Viral load was measured by quantitative RT-PCR, and expressed as the EV71 genome equivalent to TCID₅₀/mL. Data represents the mean±s.e.m. of results of duplicated experiment. (B) Suramin reduces the progeny virus yield. Data represents the mean±s.e.m. of results of two independent experiments which are duplicated.

Figure 2 Suramin blocks EV71 virus-cell attachment. (A) Time of addition assay. 10 µM suramin was added at different stage in viral infection as shown in figure. The viral load in supernatant represents the means±s.e.m. of results of experiment with three replicates, and the intracellular viral load represents the result of a single test. (B) Inhibition of viral attachment by suramin (cell-virus adsorption at 4°C). Data represents the means±s.e.m. of results of experiment with three replications.

Figure 3 Sulfonated and sulfated compounds inhibit the replication of the EV71 Fuyang573 isolate. (A) Sulfated suramin analogs inhibit EV71 infection. Data represents the means±s.e.m. of results of experiment with three replications. (B) Sulfonated and sulfated compounds not analogous to suramin inhibit EV71 infection. Data represents the means±s.e.m. of results of experiment with three replications.

Figure 4 STD NMR assay of suramin-EV71 particle binding. (A) STD NMR of suramin with the EV71 particle. ¹H (proton) NMR spectrum of suramin, shown in black, and STD NMR spectrum of suramin in complex with EV71 particles, shown in red. (B) Left: structure of suramin, labeled with proton positions and relative intensity percentages. Right: ¹H NMR spectrum of suramin, with proton numbers shown.

Figure 5 Anti-EV71 efficacy in vivo. (A) Infect 10-day-old ICR mice with 1×10⁷ TCID₅₀ (lethal dose) of the mouse-adapted EV71 strain MP10. Then inject 20 or 50 mg/kg body weight suramin by i.p. injection, twice daily for 7 days. There are 10 mice in each group. (B) Suramin at a dose of 50 mg/kg body weight decreases EV71 viremia in adult rhesus monkeys. Challenge adult monkeys with 1×10^6.5 CCID₅₀ EV71 FY-23 strain, and inject 50 mg/kg suramin i.v., on the day before virus challenge and on days 1, 3 and 5 post challenge. There are five monkeys in each group. ICR, Institute of Cancer Research; i.p., intraperitoneal; i.v., intravenously.