Name: Eric Chen High School: Canyon Crest Academy, San Diego, CA Mentor: Dr. Rommie Amaro

1. Name: Eric Chen High School: Canyon Crest Academy, San Diego, CA Mentor: Dr. Rommie Amaro Project Title: Discovery of Novel Influenza Endonuclease Inhibitors to Fight Flu Pandemic Pandemic outbreaks of highly pathogenic influenza viruses like avian strains H5N1 or H7N9 could kill millions of people before new vaccines become available. Current antiviral drugs are losing their effectiveness due to emerging resistant virus strains. Therefore, new anti-influenza drugs are urgently needed to prepare for impending flu pandemics. The influenza endonuclease is well conserved and essential for viral propagation, so inhibitors could potentially block any influenza virus. An interdisciplinary approach combining computational and biological methods was implemented to expedite discovery of new endonuclease inhibitors. Computational pharmacophore models were generated and used for virtual screening of compound libraries. A fluorescence-based assay was set up to validate virtual screening hits as endonuclease inhibitors. Molecular docking of the new inhibitors to the endonuclease active site revealed interacting residues. Structure and activity relationship analysis led to identification of additional drug leads. Consequently, a number of new, potent and structurally diverse endonuclease inhibitors have been identified with great potential to be developed into new anti-influenza drugs. The structural studies have also laid the groundwork for further drug optimization and new inhibitor design. Therefore, these findings will help combat influenza and save lives.