A preclinical study from the National Institutes of Health (NIH) suggests that tetracycline-based antibiotics like methacycline, or drugs designed to combat Alzheimer’s and inflammation, may slow infection and reduce neurological problems associated with the Zika virus.
This conclusion was based on use in mice after tests of more than 10,000 compounds. Researchers looked for drugs that would prevent Zika from reproducing by blocking the work of a protein known as NS2B-NS3 Zika virus protease. The protease releases proteins from RNA-injected cells that have been co-opted to produce more. By blocking these internal scissors, as study leader Dr. Rachel Abrams dubbed them, viruses like Zika can be counteracted.
“Around the world, the Zika outbreak produced devastating, long-term neurological problems for many children and their families,” said Dr. Avindra Nath, a senior investigator at the NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and a senior author of the study. “Although the infections are down, the threat remains. We hope these promising results are a good first step to preparing the world for combating the next potential outbreak.”
Zika is a primarily mosquito-spread virus that had its heyday in 2015 and 2016. It caused neurological disorders in adults and a developmental brain disorder in babies born from infected mothers. The virus prefers to attack stem cells in the brain.
In all, three drugs identified in this study may counteract the problems: methacycline, MK-591, or JNJ-404. Identifying these was achieved by feeding screening results into a computer and then using AI-based programs to assess what compounds would be good at blocking the protease activity. Tetracycline-based drugs are already approved by the U.S. Food and Drug Administration and are known to cross the placenta of pregnant women.
The antibiotics were not capable of fully counteracting the damage caused by Zika. Infected mice still had a lower weight than their control counterparts, whether treated with methacycline or not.
“These results suggest that tetracycline-based antibiotics may at least be effective at preventing the neurological problems associated with Zika virus infections,” Abrams said. “Given that they are widely used, we hope that we can rapidly test their potential in clinical trials.”