Scripps Research chemist Matthew Disney, PhD, and colleagues have created drug-like compounds that, in human cell studies, bind and destroy the pandemic coronavirus’ so-called “frameshifting element” to stop the virus from replicating. The frameshifter is a clutch-like device the virus needs to generate new copies of itself after infecting cells.
“Our concept was to develop lead medicines capable of breaking COVID-19’s clutch,” Disney says. “It doesn’t allow the shifting of gears.”
Viruses spread by entering cells and then using the cells’ protein-building machinery to churn out new infectious copies. Their genetic material must be compact and efficient to make it into the cells.
The pandemic coronavirus stays small by having one string of genetic material encode multiple proteins needed to assemble new virus. A clutch-like frameshifting element forces the cells’ protein-building engines, called ribosomes, to pause, slip to a different gear, or reading frame, and then restart protein assembly anew,