SummaryZika virus (ZIKV) infection in utero might lead to microcephaly and other congenital defects. In adults, cases of Guillain-Barré syndrome and meningoencephalitis associated with ZIKV infection have been reported, and no specific therapy is available so far. There is urgency for the discovery of antiviral agents capable of inhibiting viral replication and its deleterious effects. Chloroquine is widely administered 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, human brain microvascular endothelial, and neural stem cells. We demonstrated in vitro that chloroquine reduces the number of ZIKV-infected cells, virus production and cell death promoted by ZIKV infection without cytotoxic effects. Our results suggest that chloroquine is a promising candidate for ZIKV clinical trials, since it is already approved for clinical use and can be safely administered to pregnant woman.

In the last few months, an overwhelming number of people have been exposed to the Zika virus (ZIKV) in South and Central America. Here we showed, in vitro, that a Brazilian isolate impacts more severely murine neuronal progenitors and neurons than the African strain MR766. We found that the Brazilian isolate more pronouncedly inhibits neurite extension from neurospheres, alters their differentiation potential and causes neurons to have less and shorter processes. Comparing both lineages using a panel of inflammatory cytokines, we showed, with human neuroblastoma cells, that ZIKV induces the production of several inflammatory and chemotactic cytokines and once again, the Brazilian isolate had a more significant impact. Although much more needs to be studied regarding the association of ZIKV infection and brain damage during development, our study sheds some light into the differences between African and American lineages and the mechanisms by which the virus may be affecting neurogenesis.

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