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.
Identifieur interne : 003369 ( PubMed/Curation ); précédent : 003368; suivant : 003370The approved pediatric drug suramin identified as a clinical candidate for the treatment of EV71 infection-suramin inhibits EV71 infection in vitro and in vivo.
Auteurs : Peijun Ren [France] ; Gang Zou [République populaire de Chine] ; Benjamin Bailly [Australie] ; Shanshan Xu [République populaire de Chine] ; Mei Zeng [République populaire de Chine] ; Xinsheng Chen [République populaire de Chine] ; Liang Shen [République populaire de Chine] ; Ying Zhang [République populaire de Chine] ; Patrice Guillon [Australie] ; Fernando Arenzana-Seisdedos [France] ; Philippe Buchy [Cambodge] ; Jian Li [République populaire de Chine] ; Mark Von Itzstein [Australie] ; Qihan Li [République populaire de Chine] ; Ralf Altmeyer [République populaire de Chine]Source :
- Emerging microbes & infections [ 2222-1751 ] ; 2014.
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.
DOI: 10.1038/emi.2014.60
PubMed: 26038755
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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</wicri:regionArea></affiliation></author><author><name sortKey="Zou, Gang" sort="Zou, Gang" uniqKey="Zou G" first="Gang" last="Zou">Gang Zou</name><affiliation wicri:level="1"><nlm:affiliation>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031</wicri:regionArea></affiliation></author><author><name sortKey="Bailly, Benjamin" sort="Bailly, Benjamin" uniqKey="Bailly B" first="Benjamin" last="Bailly">Benjamin Bailly</name><affiliation wicri:level="1"><nlm: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.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>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</wicri:regionArea></affiliation></author><author><name sortKey="Xu, Shanshan" sort="Xu, Shanshan" uniqKey="Xu S" first="Shanshan" last="Xu">Shanshan Xu</name><affiliation wicri:level="1"><nlm:affiliation>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031</wicri:regionArea></affiliation></author><author><name sortKey="Zeng, Mei" sort="Zeng, Mei" uniqKey="Zeng M" first="Mei" last="Zeng">Mei Zeng</name><affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Diseases, Children's Hospital of Fudan University , Shanghai 201102, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Infectious Diseases, Children's Hospital of Fudan University , Shanghai 201102</wicri:regionArea></affiliation></author><author><name sortKey="Chen, Xinsheng" sort="Chen, Xinsheng" uniqKey="Chen X" first="Xinsheng" last="Chen">Xinsheng Chen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131</wicri:regionArea></affiliation></author><author><name sortKey="Shen, Liang" sort="Shen, Liang" uniqKey="Shen L" first="Liang" last="Shen">Liang Shen</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131</wicri:regionArea></affiliation></author><author><name sortKey="Zhang, Ying" sort="Zhang, Ying" uniqKey="Zhang Y" first="Ying" last="Zhang">Ying Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province</wicri:regionArea></affiliation></author><author><name sortKey="Guillon, Patrice" sort="Guillon, Patrice" uniqKey="Guillon P" first="Patrice" last="Guillon">Patrice Guillon</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland</wicri:regionArea></affiliation></author><author><name sortKey="Arenzana Seisdedos, Fernando" sort="Arenzana Seisdedos, Fernando" uniqKey="Arenzana Seisdedos F" first="Fernando" last="Arenzana-Seisdedos">Fernando Arenzana-Seisdedos</name><affiliation wicri:level="1"><nlm:affiliation>Institut National de la Santé et de la Recherche Médicale, U1108 & Viral Pathogenesis Unit, Department of Virology, Institut Pasteur , 75724 Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut National de la Santé et de la Recherche Médicale, U1108 & Viral Pathogenesis Unit, Department of Virology, Institut Pasteur , 75724 Paris</wicri:regionArea></affiliation></author><author><name sortKey="Buchy, Philippe" sort="Buchy, Philippe" uniqKey="Buchy P" first="Philippe" last="Buchy">Philippe Buchy</name><affiliation wicri:level="1"><nlm:affiliation>Virology Unit, Institut Pasteur in Cambodia , 12201 Phnom Penh, Cambodia.</nlm:affiliation><country xml:lang="fr">Cambodge</country><wicri:regionArea>Virology Unit, Institut Pasteur in Cambodia , 12201 Phnom Penh</wicri:regionArea></affiliation></author><author><name sortKey="Li, Jian" sort="Li, Jian" uniqKey="Li J" first="Jian" last="Li">Jian Li</name><affiliation wicri:level="1"><nlm:affiliation>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131</wicri:regionArea></affiliation></author><author><name sortKey="Von Itzstein, Mark" sort="Von Itzstein, Mark" uniqKey="Von Itzstein M" first="Mark" last="Von Itzstein">Mark Von Itzstein</name><affiliation wicri:level="1"><nlm:affiliation>Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland</wicri:regionArea></affiliation></author><author><name sortKey="Li, Qihan" sort="Li, Qihan" uniqKey="Li Q" first="Qihan" last="Li">Qihan Li</name><affiliation wicri:level="1"><nlm:affiliation>Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province</wicri:regionArea></affiliation></author><author><name sortKey="Altmeyer, Ralf" sort="Altmeyer, Ralf" uniqKey="Altmeyer R" first="Ralf" last="Altmeyer">Ralf Altmeyer</name><affiliation wicri:level="1"><nlm:affiliation>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031</wicri:regionArea></affiliation></author></analytic><series><title level="j">Emerging microbes & infections</title><idno type="ISSN">2222-1751</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">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.</div></front></TEI><pubmed><MedlineCitation Status="PubMed-not-MEDLINE" Owner="NLM"><PMID Version="1">26038755</PMID><DateCreated><Year>2015</Year><Month>06</Month><Day>03</Day></DateCreated><DateCompleted><Year>2015</Year><Month>06</Month><Day>03</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Print">2222-1751</ISSN><JournalIssue CitedMedium="Print"><Volume>3</Volume><Issue>9</Issue><PubDate><Year>2014</Year><Month>Sep</Month></PubDate></JournalIssue><Title>Emerging microbes & infections</Title><ISOAbbreviation>Emerg Microbes Infect</ISOAbbreviation></Journal><ArticleTitle>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.</ArticleTitle><Pagination><MedlinePgn>e62</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1038/emi.2014.60</ELocationID><Abstract><AbstractText>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.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Ren</LastName><ForeName>Peijun</ForeName><Initials>P</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zou</LastName><ForeName>Gang</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bailly</LastName><ForeName>Benjamin</ForeName><Initials>B</Initials><AffiliationInfo><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.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Xu</LastName><ForeName>Shanshan</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zeng</LastName><ForeName>Mei</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Infectious Diseases, Children's Hospital of Fudan University , Shanghai 201102, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chen</LastName><ForeName>Xinsheng</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Shen</LastName><ForeName>Liang</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Ying</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guillon</LastName><ForeName>Patrice</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Arenzana-Seisdedos</LastName><ForeName>Fernando</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Institut National de la Santé et de la Recherche Médicale, U1108 & Viral Pathogenesis Unit, Department of Virology, Institut Pasteur , 75724 Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Buchy</LastName><ForeName>Philippe</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Virology Unit, Institut Pasteur in Cambodia , 12201 Phnom Penh, Cambodia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Jian</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>State Key Laboratory of Lead Compound Research, WuXi AppTec, Co., Ltd, Shanghai 200131, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>von Itzstein</LastName><ForeName>Mark</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Institute for Glycomics, Gold Coast Campus, Griffith University , 4222 Queensland, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Qihan</ForeName><Initials>Q</Initials><AffiliationInfo><Affiliation>Institute of Medical Biology, Chinese Academy of Medicine Science , Kunming 650118, Yunnan Province, China.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Altmeyer</LastName><ForeName>Ralf</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Unit of Anti-infective Research, Institut Pasteur of Shanghai , Chinese Academy of Sciences, Shanghai 200031, China.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType></PublicationTypeList><ArticleDate 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Version="1">23295352</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>J Gen Virol. 1987 Aug;68 ( Pt 8):2183-92</RefSource><PMID Version="1">2440983</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Virus Res. 2012 Oct;169(1):22-9</RefSource><PMID Version="1">22771616</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Lab Invest. 2011 Sep;91(9):1337-50</RefSource><PMID Version="1">21555996</PMID></CommentsCorrections><CommentsCorrections RefType="Cites"><RefSource>Angew Chem Int Ed Engl. 2008;47(10):1910-2</RefSource><PMID Version="1">18232036</PMID></CommentsCorrections></CommentsCorrectionsList><OtherID Source="NLM">PMC4185360</OtherID><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">anti-viral</Keyword><Keyword MajorTopicYN="N">drug discovery</Keyword><Keyword MajorTopicYN="N">enterovirus 71</Keyword><Keyword MajorTopicYN="N">hand, foot and mouth disease</Keyword><Keyword MajorTopicYN="N">suramin</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="received"><Year>2014</Year><Month>04</Month><Day>21</Day></PubMedPubDate><PubMedPubDate PubStatus="revised"><Year>2014</Year><Month>06</Month><Day>26</Day></PubMedPubDate><PubMedPubDate PubStatus="accepted"><Year>2014</Year><Month>06</Month><Day>27</Day></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2015</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2015</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>6</Month><Day>4</Day><Hour>6</Hour><Minute>1</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">26038755</ArticleId><ArticleId IdType="doi">10.1038/emi.2014.60</ArticleId><ArticleId 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