A huge search through known drug compounds showed that a common antibiotic has been shown to be effective against Zika in vitro. Zika, which causes foetal microcephaly, preferentially attacks brain stem cells.
In order to find a compound that confers Zika protection, the researchers searched for drugs that prevent virus reproduction by blocking the activity of a protein called NS2B-NS3 Zika virus protease. This protease acts to assemble the components of new Zika viruses from protein produced by the virus’ RNA injection into a cell.
“Proteases act like scissors. Blocking protease activity is an effective strategy for counteracting many viruses,” said study leader Rachel Abrams, PhD. “We wanted to look as far and wide as possible for drugs that could prevent the protease from snipping the Zika virus polyprotein into its active pieces.”
To find out which compounds blocked the protease, hundreds of assays were conducted against three different libraries.
An initial screen of 2 000 compounds showed that common tetracycline-based antibiotic drugs, such as methacycline were able to block the protease.
A larger screen of 10 000 compounds found potential candidates in an investigational anti-inflammatory medicine, MK-591, and a failed anti-Alzheimer’s disease drug, JNJ-404.
Finally, 130 000 compounds were screened virtually, with machine learning being used to investigate what made a good candidate.
The candidate compounds were shown to reduce Zika infections of brain stem cells in vitro.
As methacycline is known to cross the placental barrier, this emerged as a promising candidate to treat pregnant women infected with the virus. However in mouse models, treatment with methacycline only partially protected the brains of newborn mice.
“These results suggest that tetracycline-based antibiotics may at least be effective at preventing the neurological problems associated with Zika virus infections,” said Dr Abrams. “Given that they are widely used, we hope that we can rapidly test their potential in clinical trials.”
Source: News-Medical.Net
