New ideas for improving the development of drugs and vaccines targeting Zika

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.
A Stanford team's findings could lead to a drug that targets multiple flaviviruses while reducing the risk that they become drug-resistant.

Stanford University scientists have devised an approach that combats Zika by targeting a protein in the host cell, preventing the virus from replicating. It's one of two recent developments aimed at Zika that could boost ongoing efforts to treat and prevent the mosquito-born virus.

Studying the cells that viruses infect, Stanford's Jan Carette, Ph.D., and his team previously found that flaviviruses like Zika rely on their hosts' oligosaccharyltransferase (OST) complex, a part of the cell that adds sugar molecules to proteins. If a cell does not have this component, it cannot be infected by a flavivirus. 

In their new study, which appears in the journal Cell Reports, Carette's team worked with Yale University scientists who had developed a drug, NGI-1, to curb the activity of the OST complex. It could prove effective against not just Zika virus, but all the other viruses in its family, they believe.

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They found that the sooner they administered the drug to Zika- or dengue-infected cells, the better it worked. NGI-1 reduced infection by 99% when used to treat cells immediately after infection. It cut infection by 80% if administered 24 hours after infection. The treatment was effective in cells infected with West Nile and yellow fever virus, as well as four types of dengue and multiple strains of Zika. 

"Generally, when you develop a drug against a specific protein in dengue virus, for instance, it won't work for yellow fever or Zika, and you have to develop new antivirals for each," said Carette, an assistant professor of microbiology and immunology at Stanford and senior author of the study. "Here, by targeting the host rather than a specific virus, we've been able to take out multiple viruses at once." 

Besides being a solution for multiple viruses, the approach tackles the issue of drug resistance. Because the drug is geared toward a piece of the host cell, the flaviviruses it targets are "unlikely" to develop resistance to it, Carette said. 

RELATED: One step closer to a Zika vaccine for pregnant women 

On the vaccine front, a Harvard Medical School-led team tested the longevity of three proposed platforms for a Zika vaccine—a DNA vaccine, an inactivated virus vaccine and a vaccine based on an adeno-associated virus (AAV). 

In previous studies, researchers had mounted a Zika challenge soon after vaccination, when animal subjects are at peak immunity. So the Harvard team waited one year after rhesus monkeys were vaccinated to test their immune response.

RELATED: Takeda pushes U.S.-backed Zika vaccine into the clinic 

The researchers found that one dose of the AAV-based vaccine protected 100% of subjects one year following vaccination. Two doses of purified, inactivated virus protected 75% of the animals, while two shots of a DNA vaccine failed to protect 71% of the subjects, which had Zika virus in their blood, at one year. 

The work, published in Science Translational Medicine, shows that one-year protection against Zika is possible in rhesus monkeys with a single-dose vaccine. But the results don't bode well for Inovio Pharma and the Wistar Institute, which are both developing synthetic DNA vaccines. 

There is no approved vaccine or treatment for Zika, and the same goes for many other flaviviruses. Like the Stanford team, researchers from Washington University in St. Louis are looking to change this by targeting host cells. Last year, they pinpointed a single gene that, if switched off in human and insect cells, halted the spread of Zika infection without harming the cell itself. Scientists at Sanford Burnham Prebys are working to curtail Zika infection by attacking the virus' protease function

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