Chloroquine inhibits Zika Virus infection in different cellular models

Abstract

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.

The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

“…Several ongoing studies have demonstrated the anti-ZIKV activity of clinically approved drugs10111213141518. Here, we show that sofosbuvir-triphosphate inhibits ZVRP in a dose-dependent fashion.…”

“…Some broad-spectrum antivirals, such as interferons (IFNs), ribavirin and favipiravir, are not suitable for use against ZIKV because they can be harmful to pregnant women9. Alternatively, others have studied the use of Food and Drug Administration (FDA)-approved small molecule drugs against ZIKV101112131415. Overall, these drugs might exert their anti-ZIKV activity at least in part by interfering with the cellular pathways important for ZIKV replication101112131415.…”

The clinically approved antiviral drug sofosbuvir impairs brazilian zika virus replication

“…Interferons (IFNs) are abortive, ribavirin and favipiravir are teratogenic (9), (10). Currently, at least three studies have been published in the field of small molecules inhibitors of anti-ZIKV replication (11–13). In these studies, the authors used in their experimental infections the African ZIKV (ZIKV AFR ) as a prototype (11–13).…”

“…Currently, at least three studies have been published in the field of small molecules inhibitors of anti-ZIKV replication (11–13). In these studies, the authors used in their experimental infections the African ZIKV (ZIKV AFR ) as a prototype (11–13). Importantly, it has been shown that ZIKV AFR is more virulent than the ZIKV strain circulating in Brazil (ZIKV BRA ) (14), meaning that one might neglected a promising clinically approved compound by screening libraries of compounds over ZIKV AFR .…”

Zika Virus in the Human Placenta and Developing Brain: Cell Tropism and Drug Inhibition

“…U87 cells infected with ZIKV show a profound CPE at 48 hpi, with significant cell death occurring at 72 hpi (data not shown). Recent reports suggested that chloroquine, a drug historically used to treat or prevent malaria, could protect cells against ZIKV-induced death 20 . We observed a modest protective effect against ZIKV-induced CPE using chloroquine at 2-10 μM, but observed dramatic toxicity of the drug at over 10 μM (data not shown).…”