Harvard Medical School scientists have found a compound that in laboratory dishes blocks the dengue virus in two ways, raising hopes for a future drug whose dual activity could suppress the otherwise likely emergence of drug resistance.
The HMS team, led by Priscilla Yang, an HMS associate professor of microbiology and immunobiology, reported its findings April 21 in Cell Chemical Biology.
Spread by mosquitoes, dengue belongs to the same family of viruses as Zika, whose emerging strain has just been linked by the U.S. Centers for Disease Control and Prevention to severe birth defects. Like Zika, dengue virus has no antiviral drugs to prevent illness or stop its spread.
Dengue virus infects more than 300 million people a year worldwide, causing no symptoms in some people but flu-like misery or dangerous hemorrhagic fevers in others.
The compound found by Yang’s team, GNF-2, keeps the dengue virus from infiltrating and overwhelming cells in the body. It does this by blocking its known kinase target inside the cell and by also inhibiting a viral target found on the surface of the virus. Yang considers the discovery of GNF-2 to be serendipitous.
“We had screened a library of known kinase inhibitors and had a ‘problem compound’ where we could not explain all the antiviral activity that we were seeing based on just the effect it had on the host kinase it normally targets,” Yang said.