Widely used malaria drug may shield fetuses from Zika infection

As of September, the Zika virus was officially on U.S. soil. Local businesses must do everything they can to keep travelers feeling safe, so they remember to come back.
Preventing Zika virus from invading the placenta is a key focus of researchers at Washington University in St. Louis.

The neurological damage caused by the mosquito-born virus Zika occurs when babies are in the womb, so it’s no surprise scientists have been searching for ways to create barriers that shield fetuses from infection. Toward that end, a team of researchers at the Washington University School of Medicine in St. Louis has been focusing on a key element of fetal development called autophagy, which is the process by which cells dispose of waste and unwanted microbes to create a placental barrier that keeps infectious invaders away from developing infants.

Now, they’ve found a way to manipulate autophagy to lower the risk of Zika infection in developing fetuses, using one of the world’s best-known drugs: the malaria treatment hydroxychloroquine. The research team discovered that hydroxychloroquine, which is listed as an essential medicine by the World Health Organization, blocks the transmission of Zika to the fetus, according to a press release. The research was published in The Journal of Experimental Medicine.

The scientists started by infecting human placental cells with Zika, so they could observe how the virus invades the womb. They tried boosting autophagy with drugs, but that didn’t work—in fact, it seemed to allow the virus to infect even more cells.

"It appears that Zika virus takes advantage of the autophagy process in the placenta to promote its survival and infection of placental cells," said Bin Cao, a postdoctoral fellow and co-author of the study.

So Cao and colleagues tried suppressing autophagy instead. That worked. And when they infected mouse models of weak autophagy with Zika, they discovered the pregnant animals had a viral load in the placenta 10 times lower than normal mice did.

Hydroxychloroquine is known to suppress autophagy. So the researchers repeated the mouse experiment, dosing the animals with either the drug or a placebo after Zika infection. They found significantly less virus in the placentas of the drug-treated mice, even though the untreated and treated animals had about the same amount of Zika virus in their bloodstreams, according to the statement.

Several other approaches aimed at protecting the placenta from Zika are being examined. In May, scientists at Sanford Burnham Prebys announced they identified a compound that blocks the proteases the virus needs to replicate, for example. A multi-institutional effort that includes scientists from Washington University involves studying an antibody that seems to reduce the transmission of the virus from mother to fetus, and yet another WashU team is using the gene-editing technique CRISPR to identify genes that can be switched off to prevent Zika from spreading in the body.

The discovery that hydroxychloroquine may shield against Zika is exciting, to be sure, considering that the drug—which was first approved in the U.S. in the 1950s and is marketed under several brand names, including Plaquenil—wholesales for less than $7 a month in parts of the developing world. What’s more, it has been used in pregnant women for short periods of time. But the Washington University researchers caution that more research will be needed to determine whether the malaria drug is safe to be used throughout the entire term of a pregnancy.