Medical Discovery Institute
Alexey Terskikh, PhD Photo courtesy of Sanford Burnham Prebys
Preclinical research suggests a drug used to prevent and treat malaria may also be effective against Zika virus.
Investigators found that chloroquine can protect human neural progenitors from infection with Zika virus.
The drug also decreased Zika-induced mortality in one mouse model and hindered transmission of Zika virus from mother to fetus in another mouse model.
Alexey Terskikh, PhD, of Sanford Burnham Prebys Medical Discovery Institute in La Jolla, California, and his colleagues conducted this research and disclosed the results in Scientific Reports.
“There is still an urgent need to bolster our preparedness and capacity to respond to the next Zika outbreak,” Dr Terskikh said. “Our latest research suggests the antimalaria drug chloroquine may be an effective drug to treat and prevent Zika infections.”
The investigators first found that chloroquine reduced Zika infection in primary human fetal neural precursor cells.
The team also discovered that chloroquine reduced the percentage of Zika-positive cells and the level of apoptosis in neurospheres derived from human induced pluripotent stem cells.
The investigators then tested chloroquine in AG129 mice, which lack receptors for type I and II interferons and have been used to model Zika virus infection.
Some of these mice received chloroquine (50 mg/kg/day) in their drinking water for 2 days and were then infected with Zika virus. The mice continued to receive chloroquine at the same dose for 5 days and then received 5 mg/kg/day until the end of the experiment.
Control AG129 mice were infected with Zika virus and received regular drinking water.
Compared to controls, chloroquine-treated mice had significantly prolonged survival and a significant reduction in Zika-induced weight loss (P<0.01 for both).
Next, the investigators used SJL mice to study horizontal and vertical transmission of Zika. They observed successful transmission of the virus from males to females and from mothers to pups.
The team then analyzed the effects of chloroquine on fetal transmission of Zika. Pregnant SJL mice were infected with Zika and given drinking water containing chloroquine (30 mg/kg/day) starting on day E13.5. The mice were euthanized on E18.5, and maternal blood and fetal brain samples were collected.
Chloroquine treatment resulted in a roughly 20-fold reduction in Zika virus titers in the maternal blood and fetal brain.
“Although chloroquine didn’t completely clear Zika from infected mice, it did reduce the viral load, suggesting it could limit the neurological damage found in newborns infected by the virus,” Dr Terskikh said.
“Chloroquine has a long history of successfully treating malaria, and there are no reports of it causing birth defects. Additional studies are certainly needed to determine the precise details of how it works. But given its low cost, availability, and safety history, further study in a clinical trial to test its effectiveness against Zika virus in humans is merited.”
