title: Chloroquine, an Endocytosis Blocking Agent, Inhibits Zika Virus Infection in Different Cell Models.
abstract: Zika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. Since no specific therapy is available thus far, there is an urgent need for the discovery of agents capable of inhibiting its viral replication and deleterious effects. Chloroquine is widely used as an antimalarial drug, anti-inflammatory agent, and it also shows antiviral activity against several viruses. Here we show that chloroquine exhibits antiviral activity against ZIKV in Vero cells, human brain microvascular endothelial cells, human neural stem cells, and mouse neurospheres. We demonstrate that chloroquine reduces the number of ZIKV-infected cells in vitro, and inhibits virus production and cell death promoted by ZIKV infection without cytotoxic effects. In addition, chloroquine treatment partially reveres morphological changes induced by ZIKV infection in mouse neurospheres.
authors.affiliation: Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. digodelvecchio@gmail.com.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Delvecchio
authors.affiliation: Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. luizahiga@gmail.com.
authors.forename: Luiza M
authors.initials: LM
authors.lastname: Higa
authors.affiliation: Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. paulapezzuto81@gmail.com.
authors.forename: Paula
authors.initials: P
authors.lastname: Pezzuto
authors.affiliation: Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. analuvaladao@gmail.com.
authors.forename: Ana Luiza
authors.initials: AL
authors.lastname: Valadão
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. ppgarcez@gmail.com.|D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil. ppgarcez@gmail.com.
authors.forename: Patrícia P
authors.initials: PP
authors.lastname: Garcez
authors.affiliation: Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. fabiolimonte@gmail.com.
authors.forename: Fábio L
authors.initials: FL
authors.lastname: Monteiro
authors.affiliation: D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil. erickloiola@lance-ufrj.org.
authors.forename: Erick C
authors.initials: EC
authors.lastname: Loiola
authors.affiliation: Department of Immunology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. aadias2005@yahoo.com.br.
authors.forename: André A
authors.initials: AA
authors.lastname: Dias
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. fabiojms@icb.ufrj.br.
authors.forename: Fábio J M
authors.initials: FJ
authors.lastname: Silva
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. mtaliota@wisc.edu.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Aliota
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. eacaine@wisc.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Caine
authors.affiliation: Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA. jorge.osorio@wisc.edu.
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Osorio
authors.affiliation: Department of Immunology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. mariabellioufrj@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Bellio
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA. dhoconno@wisc.edu.
authors.forename: David H
authors.initials: DH
authors.lastname: O'Connor
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. srehen@lance-ufrj.org.|D'Or Institute for Research and Education (IDOR), Rio de Janeiro 22281-100, Brazil. srehen@lance-ufrj.org.
authors.forename: Stevens
authors.initials: S
authors.lastname: Rehen
authors.affiliation: Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. santanarnt@gmail.com.
authors.forename: Renato Santana
authors.initials: RS
authors.lastname: de Aguiar
authors.affiliation: Istituto Superiore di Sanità, Deptartment of Infectious Diseases, 299 Viale Regina Elena, 00161 Rome, Italy. ansavari@yahoo.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Savarino
authors.affiliation: Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. lcampanati@gmail.com.
authors.forename: Loraine
authors.initials: L
authors.lastname: Campanati
authors.affiliation: Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil. atanuri@biologia.ufrj.br.
authors.forename: Amilcar
authors.initials: A
authors.lastname: Tanuri
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D002738:Chloroquine / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects*; D006801:Humans; D051379:Mice; D000071244:Zika Virus / Q000187:drug effects* / Q000502:physiology*; D000071243:Zika Virus Infection / Q000821:virology*
chemical_list: D000998:Antiviral Agents; D002738:Chloroquine
keywords: Zika virus; antiviral; chloroquine; microcephaly; neural stem cell