title: 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.
authors.affiliation: Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China ; Université Paris Diderot, Sorbonne Paris Cité, Cellule Pasteur , 75013, Paris, France ; Institut National de la Santé et de la Recherche Médicale, U1108 & Viral Pathogenesis Unit, Department of Virology, Institut Pasteur , 75724 Paris, France.
authors.forename: Peijun
authors.initials: P
authors.lastname: Ren
authors.affiliation: Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Zou
authors.affiliation: Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China ; Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland, Australia.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bailly
authors.affiliation: Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, Children's Hospital of Fudan University , Shanghai 201102, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zeng
authors.affiliation: State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland, Australia.
authors.forename: Patrice
authors.initials: P
authors.lastname: Guillon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1108 & Viral Pathogenesis Unit, Department of Virology, Institut Pasteur , 75724 Paris, France.
authors.forename: Fernando
authors.initials: F
authors.lastname: Arenzana-Seisdedos
authors.affiliation: Virology Unit, Institut Pasteur in Cambodia , 12201 Phnom Penh, Cambodia.
authors.forename: Philippe
authors.initials: P
authors.lastname: Buchy
authors.affiliation: State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: von Itzstein
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
authors.affiliation: Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ralf
authors.initials: R
authors.lastname: Altmeyer
keywords: anti-viral; drug discovery; enterovirus 71; hand, foot and mouth disease; suramin