GNF-2 Inhibits Dengue Virus by Targeting Abl Kinases and the Viral E Protein.

ABSTRACT: Dengue virus infects more than 300 million people annually, yet there is no widely protective vaccine or drugs against the virus. Efforts to develop antivirals against classical targets such as the viral protease and polymerase have not yielded drugs that have advanced to the clinic. Here, we show that the allosteric Abl kinase inhibitor GNF-2 interferes with dengue virus replication via activity mediated by cellular Abl kinases but additionally blocks viral entry via an Abl-independent mechanism. To characterize this newly discovered antiviral activity, we developed disubstituted pyrimidines that block dengue virus entry with structure-activity relationships distinct from those driving kinase inhibition. We demonstrate that biotin- and fluorophore-conjugated derivatives of GNF-2 interact

SUBMITTER: Clark MJ 

PROVIDER: S-EPMC4865888 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature