Antimalarial Drug Repurposed to Treat and Prevent Zika Transmission

Chloroquine’s (CQ) success at treating and preventing the spread of malaria is almost immeasurable. The compound was initially developed prior to World War II and initially showed amazing efficacy against the parasitic disease. In combination with vector (mosquito) control efforts to stymie transmission rates, using compounds such as DDT, the World Health Organization (WHO) launched initiatives to eradicate malaria globally. Unfortunately, by the mid-1970’s, resistance to CQ had reached a point where the drug was no longer effective in many parts of Southeast Asia and sub-Saharan Africa.

Yet, CQ’s initial effectiveness had researchers searching for other uses of the compound – uncovering efficacy in treating diseases such as rheumatoid arthritis and lupus. These findings, plus its extremely low-cost to manufacture, are why the drug remains on the WHO’s List of Essential Medicines.

Now, researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) and UC San Diego School of Medicine may have discovered a new use for the long-standing compound – treating Zika. The investigators examined the effect of CQ in human brain organoids and pregnant mice infected with Zika and found the drug markedly reduced the amount of virus in maternal blood and neural progenitor cells in the fetal brain. Findings from the new study were published in Scientific Reports in an article entitled “Repurposing of the Anti-Malaria Drug Chloroquine for Zika Virus Teatment and Prophylaxis.”

Zika virus remains a major global health risk. In most adults, Zika causes mild flu-like symptoms. But in pregnant women, the virus can cause serious birth defects in babies – including microcephaly – a neurological condition in which newborns have unusually small heads and fail to develop properly. There is no treatment or way to reverse the condition. CQ has a long history of safe use during pregnancy. (Related article: Zika Biomarkers Could Lead to Prenatal Diagnostic)

“There is still an urgent need to bolster our preparedness and capacity to respond to the next Zika outbreak,” remarked senior study investigator Alexey Terskikh, Ph.D., associate professor at SBP. “Our latest research suggests the antimalaria drug CQ may be an effective drug to treat and prevent Zika infections.”

Administering CQ to mice through drinking water in dosages equivalent to acceptable levels used in humans, the research team showed that the drug extended the lifespan of the rodents infected with lethal doses of the Zika virus.

“Our research is the first to study Zika infection in a mouse model that transmits the virus in a way similar to humans,” explained co-senior study investigator Alysson Muotri, Ph.D., professor, and director of the Stem Cell Program at UC San Diego. “Until now, researchers used a mouse strain that is deficient in interferon – a signaling protein that heightens antiviral defenses. Those mice actually die from Zika infection, making it difficult to study the natural transmission of the virus from father and mother to fetus and to assess the effect of this transmission on the newborns.”

“We believe our mouse model more accurately represents the way Zika virus infects men, women, and babies while in the womb,” added Dr. Terskikh. “Although CQ 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.”

The positive response infected mice had when treated with CQ has the researchers reevaluating current drug designs as well as public health initiatives that could be considered to help stem the rapid rise of Zika cases.

“In the 1950’s, the Brazilian health agencies added CQ into cooking salt and distributed it to the population in endemic areas as an effective way of spreading the inexpensive antimalarial drug as a prophylactic on a wide scale,” Dr. Muotri noted. This strategy was known as Pinotti’s method, named after its originator Dr. Mario Pinotti. It might be worth considering this medicated salt program one more time in Brazil.”

The researchers were encouraged by their findings, but caution against overinterpretation of the results as they noted many more studies need to be employed to determine CQ’s true effectiveness against Zika.

“CQ has a long history of successfully treating malaria, and there are no reports of it causing birth defects,” Dr. Terskikh concluded. “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.”