Fighting Zika: Teaching an old drug new tricks

A once abandoned drug could be used to fight Ebola, Zika and dengue viruses, according to scientists from Stanford University

The team of scientists used the drug, which was originally developed by GlaxoSmithKline (GSK), to help human cells fight two viruses in a lab dish.

Stanford University said the scientists are using the drug to boost the human body's ability to resist the virus rather than taking on the virus directly. The work was published March 28 in Nature Chemical Biology.

Chaitan Khosla, a professor of chemistry and of chemical engineering who was one of the senior authors on the paper, said the way the drug works suggests that it could be broadly effective against viruses that use RNA rather than DNA as their genetic material.

"Most of the really nasty viruses use RNA," Khosla said, including Ebola, dengue, Zika and Venezuelan equine encephalitis virus (VEEV).

The university said that the scientists had known about the drug being developed by GSK that helped human cells fight viruses. However, after a few initial publications the drug got shelved.

Khosla thought that it might be possible to understand the drug's mechanism and possibly improve upon it, resurrecting the drug from the shelves and delivering it to patients, according to the university.

Chemistry graduate student Richard Deans started testing the drug on human cells in a lab dish and found that it enabled the cells to fight off viruses that cause either dengue or VEEV, both of which normally kill the cells.

Although the drug was effective at fighting the viruses, Deans found that over time the drug also caused the human cells to stop dividing.

The team learned that the drug interferes with a protein that is crucial for making the individual building blocks of RNA, the genetic code for the virus. Without RNA the virus can't make more of itself, which explains why the drug was so effective, according to Stanford University.

Cells also need RNA and can get RNA building blocks in two ways – by making them or by importing them from the bloodstream.

The drug blocked the cell's ability to make the RNA building blocks but the same building blocks needed for RNA synthesis are also needed to make DNA, the cell's genetic code that it replicates with each division. When a cell runs out of DNA building blocks, it can no longer divide.

To counter the effects of the drug the scientists fed cells a slightly different building block that can only be used to generate DNA, not RNA, enabling the cells to successfully fight off both dengue and VEEV and keep dividing normally.

Khosla said they plan to test the drug combination against many different RNA viruses and hopes it might become among the first broad antiviral strategies for human disease.

He also cautioned that at this stage the team has only shown that the drug is effective in a lab dish and on certain viruses. They plan to test their strategy in animals next to learn whether it is safe and to understand which viral diseases it is most effective against.