STANFORD, Calif., March 28 — Researchers found a drug discarded by the company GlaxoSmithKline because of side effects during clinical trials helped human cells fight off two viruses, according to a new study.
The drug GSK983 helped cells in the lab fight off the viruses that cause dengue fever and Venezuelan equine encephalitis virus, or VEEV, suggesting it could be used to develop a broad antiviral.
While the drug helped the cells prevent infection, it also prevented them from dividing — and they died — suggesting another drug needs to be pared with GSK983 to keep cells’ ability to divide intact.
The researchers performed a genome-wide screen on the viruses, searching for methods to prevent them from infection cells. Already aware of GSK983, the researchers thought the drug could prevent the RNA-based viruses from replicating inside cells.
“The genome-wide screen carried out in the Bassik lab was really powerful, because it gave us insights into future research strategies,” Richard Deans, a researcher at Stanford University, said about the method of genomic screening developed by Dr. Michael Bassik in a press release. “I think going forward his strategy will be much more heavily used.”
For the study, published in the journal Nature Chemical Biology, researchers tested GSK983 on human cells, finding it fought off the viruses, but died days later because the drug then stopped them from dividing.
The reason for this, researchers said, is that blocking a protein key to making the building blocks of RNA prevents the viruses from copying their RNA, but cells, which also need RNA, are also prevented from creating those building blocks — which are also required to make DNA, necessary for division.
To solve this problem, the researchers introduced a slightly different building block that could only be used by the cells for DNA. The cells then fought off both viruses and continued dividing normally.
Future studies will be focused on identifying a second drug to prevent the cell death side effect, with the long-term goal of a broad-based drug to prevent infection from similar RNA-based mosquito-borne disease.