Drugs that activate a cell’s pathways to inhibit the replication of pathogens were revealed in a recent study to be a promising approach to treating dangerous infections caused by Zika virus, dengue fever, and chikungunya.
The study was conducted by researchers at Oregon Health and Science University (OHSU), with results being published in a recent issue of the journal mBio.
The three viruses, all of which are members of the flavivirus family of viruses, are spread by the same family of mosquito and elicit similar symptoms.
OHSU Virologist Victor R. DeFilippis predicted that cellular innate immune responses may be pharmacologically harnessed to block infections as a kind of antiviral immunotherapy.
“The tools that we need to fight off virus infection are programmed into our cells as a result of evolution,” DeFilippis, who led the study, said. “I think that’s a potentially lost opportunity for the identification of novel broad-spectrum antiviral strategies.”
DeFilipis and his research team first began researching a small molecule, which they called AV-C, that triggers cellular defenses by activating the interferon system. In a series of experiments, the research team treated human fibroblasts with AV-C and then infected the cells with one of the three viruses after waiting for a period of approximately six hours. The drug was found to keep the viral presence low, leading the researchers to determine that AV-C initiates a cellular state antagonistic to replication.
The research team then examined whether the molecule had the potential to stop infection when administered after Zika and chikungunya infection. AV-C was found to block Zika infection when administered as late as 16 hours after being administered. For chikungunya, however, the molecule did not block viral replication when given just two hours post-infection.
DeFilippis said his team will now need to examine the clinical utility of the drug in animal models, such as nonhuman primates.
“There are potential drugs out there we haven’t really taken a look at,” DeFilippis said. “We’re characterizing a number of other agents that are just as promising, and many are even more promising.”