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

Abstract

Enterovirus 71 (EV71) causes severe central nervous system infections, leading to cardiopulmonary complications and death in young children. There is an urgent unmet medical need for new pharmaceutical agents to control EV71 infections. Using a multidisciplinary approach, we found that the approved pediatric antiparasitic drug suramin blocked EV71 infectivity by a novel mechanism of action that involves binding of the naphtalentrisulonic acid group of suramin to the viral capsid. Moreover, we demonstrate that when suramin is used in vivo at doses equivalent to or lower than the highest dose already used in humans, it significantly decreased mortality in mice challenged with a lethal dose of EV71 and peak viral load in adult rhesus monkeys. Thus, suramin inhibits EV71 infection by neutralizing virus particles prior to cell attachment. Consequently, these findings identify suramin as a clinical candidate for further development as a therapeutic or prophylactic treatment for severe EV71 infection.

• anti-viral
• drug discovery
• enterovirus 71
• hand, foot and mouth disease
• suramin

We thank Dr Lianfeng Zhang (Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences, Beijing, China) for performing the in vivo EV71 mouse efficacy experiment and Dr Haiheng Dong (WuXi AppTec, Shanghai, China) for carrying out the Ether-à-go-go-related gene channel assay. This research was partially supported by funding from the National Basic Research Program of China (973 program, 2012CB724500), Natural Science Foundation of China (31270204), Science and Technology Commission of Shanghai Municipality (12431900503), Li Ka Shing foundation to Ralf Altmeyer. Gang Zou is supported by the Sanofi-Shanghai Institutes for Biological Sciences Scholarship Program. Benjamin Bailly gratefully acknowledges the award of a Griffith University Postgraduate Scholarship and a doctoral grant from the Calmette program of the Insititut Pasteur International Division.

Note: Supplementary Information for this article can be found on Emerging Microbes & Infections' website (http://www.nature.com/lsa/).