Yeast-Based High-Throughput Screens for Inhibitors of Key Flaviviral Enzymes

With no clinically approved antiviral therapy available for treatment of flavivirus infections, the development of efficient vaccines and antiviral agents for prevention and treatment of infections is an urgent health priority. A combination of structure-based in silico models, in vitro and cell-based assays has led in the last decade to the identification of promising new compounds with antiviral properties, for the most part targeting one of the key enzymatic functions essential to the life cycle of these viruses. In this context development of highly-performing assays with increased screening capacity is seen as a valuable tool needed to extend screening campaigns. Agave BioSystems proposes to develop yeast-based assays for the high-throughput screening of chemical inhibitors of the flaviviral NS2B/NS3 protease activity and both the RNA methyltransferase activity and RNA polymerase activity of NS5. Key advantages of yeast-based assays are the direct screening in a cellular environment, strong statistical performance in microplate formats with no reagent aging, and most importantly extremely simple and cost-effective scalability for high-throughput campaigns.