Researchers have discovered that a drug that was discarded by pharmaceutical company GlaxoSmithKline due to its side effects that were observed in clinical trials helps human cells fight disease-causing viruses.
In lab tests, the drug GSK983 was found to help cells fight mosquito-borne viruses that cause dengue fever and Venezuelan equine encephalitis virus (VEEV), which can infect horses and kill people.
Results of the experiments suggest that this abandoned drug may be used to develop treatments that could fight other viruses such as those that cause Ebola and Zika. These two diseases pose threat to populations worldwide but remain elusive to effective treatments.
For the study, Chaitan Khosla, from Stanford University, and colleagues tested GSK983 on human cells and found that it helped fight viral infection. Unfortunately, the drug also prevented the cells from dividing so they died days later.
The researchers eventually learned that this happened because the drug disrupts a protein that plays a crucial role in making individual blocks of RNA. Without RNA, viruses are not able to replicate themselves which is why the drug was very effective in fighting viruses.
The cells, however, also need RNA so they also die when they do not get this building block that is also needed to produce DNA.
To solve this problem, Khosla and colleagues fed the cells with a slightly different building block that can only be used to generate DNA but not RNA. With this new building block, the cells were able to fight off the viruses while still able to divide normally.
The result offers clues on how the drug can be made less toxic in animals and even people.
"We found that exogenous deoxycytidine markedly reduced GSK983 cytotoxicity but not antiviral activity, providing an attractive new approach to improve the therapeutic window of DHODH inhibitors against RNA viruses," the researchers wrote in their study, which was published in the journal Nature Chemical Biology on March 28.
The researchers plan to conduct tests on animals and to test the drug combo against different RNA viruses to determine which of the viruses the strategy is able to fight most effectively, since many of the most deadly and hard-to-combat viruses have RNA as their genetic structure.
