Targeting Exonuclease Resistant RNA to Develop Zika Virus Therapeutics

Project Summary Abstract Outbreaks of Zika VirusZIKVhave been recorded in Africathe AmericasAsiaand the Pacificand despite significant resources being dedicated to combat ZIKV proliferationthere is no known cureMany mosquitoborne flavivirus such as ZIKVDengue virusYellow Fever virusand West Nile virus have structuredUTRsStructured RNA elements in theUTRs allow the virus to resist degradation by host exonucleases during infection leading to the production of noncoding subgenomic flavivirus RNAswhich are directly linked to cytopathic and pathologic effects by dysregulating RNA decay pathways and binding cellular proteins important for antiviral responseWe aim to develop small molecules that target the ZIKV exonuclease resistant RNA to promote ZIKV genome degradation by host exonucleases and inhibit viral proliferation and infectionSuccessfully demonstrating that flaviviral exonuclease resistant RNAs can be targeted by small molecules to inhibit viral proliferation and infection has the potential to create an entirely new field of anti flavivral drug discovery and lead to the development of broad spectrum anti flaviviral therapeutics Project Narrative Outbreaks of ZIKV have been recorded in Africathe AmericasAsiaand the Pacificand despite significant resources being dedicated to combat ZIKV proliferationthere is no known cureWe aim to develop small molecules that target the ZIKV exonuclease resistant RNA to promote ZIKV genome degradation by host exonucleases and inhibit viral proliferation and infectionSuccessfully demonstrating that flaviviral exonuclease resistant RNAs can be targeted by small molecules to inhibit viral proliferation and infection has the potential to create an entirely new field of anti flavivral drug discovery and lead to the development of broad spectrum anti flaviviral therapeutics