Building a Molecular Weapon in the Fight Against Zika
By LIDA TUNESI
The Zika virus, first identified in 1947, made headlines in 2015 with an outbreak in Brazil, followed by cases elsewhere in Latin America, the Caribbean, and the U.S. The virus causes microcephaly and other birth defects in the children of pregnant, infected mothers. No antiviral drug has been specifically approved to treat it.
Now, researchers from Hunter College and the Advanced Science Research Center (ASRC) at The Graduate Center, CUNY, have developed a series of molecules that have strong anti-Zika activity while showing low toxicity toward animal cells.
The paper, authored by Ph.D. student Fernando Bravo, Hunter College undergraduates Milan Shlain and Yasir Naeem, and Professor Adam Braunschweig of Hunter College and the ASRC, appears in the Journal of Medicinal Chemistry.
“What makes this project unique, in addition to the very potent anti-Zika activity, is the mechanism of action,” Braunschweig said. “This is one of the first reports of a molecule that works by inhibiting virus uptake into the cell.”
All viruses and eukaryotic cells, which include plant and animal cells, have carbohydrates attached to their surfaces. The carbohydrates act like ID tags, helping cells recognize each other via carbohydrate receptors. This same method helps viruses gain entry into cells.
To prevent this interaction, the researchers created synthetic carbohydrate receptors. The receptors latch on to surface carbohydrates, blocking the virus’s point of entry. The team doesn’t yet know whether the receptors are binding to carbohydrates on the virus or on the cell, but either way is effective.
The strategy of using synthetic carbohydrate receptors, Braunschweig said, also has potential in developing antibacterial, antiparasitic, and anticancer therapies.
The researchers are now working on the next generation of molecules—improving the current class by using chemical knowledge gained in developing the first—and hope to someday test them in animal trials.