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EBioMedicine ; 24: 189-194, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29033372

RESUMO

Zika virus (ZIKV) has become a global public health emergency due to its rapidly expanding range and its ability to cause severe congenital defects such as microcephaly. However, there are no FDA-approved therapies or vaccines against ZIKV infection. Through our screening of viral entry inhibitors, we found that chloroquine (CQ), a commonly used antimalarial and a FDA-approved drug that has also been repurposed against other pathogens, could significantly inhibit ZIKV infection in vitro, by blocking virus internalization. We also demonstrated that CQ attenuates ZIKV-associated morbidity and mortality in mice. Finally, we proved that CQ protects fetal mice from microcephaly caused by ZIKV infection. Our methodology of focusing on previously identified antivirals in screens for effectiveness against ZIKV proved to be a rapid and efficient means of discovering new ZIKV therapeutics. Selecting drugs that were previously FDA-approved, such as CQ, also improves the likelihood that they may more quickly reach stages of clinical testing and use by the public.


Assuntos
Cloroquina/administração & dosagem , Microcefalia/prevenção & controle , Infecção por Zika virus/tratamento farmacológico , Animais , Linhagem Celular , Chlorocebus aethiops , Cloroquina/farmacologia , Modelos Animais de Doenças , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Camundongos , Microcefalia/mortalidade , Microcefalia/virologia , Células Vero , Internalização do Vírus/efeitos dos fármacos , Zika virus/efeitos dos fármacos , Zika virus/fisiologia , Infecção por Zika virus/complicações , Infecção por Zika virus/mortalidade
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