A future influenza epidemic caused by zoonotic transmission of a new influenza strain is inevitable, and there is a need for cheap and safe antiviral compounds that are effective against pandemic influenza. This project will use the XCHEM fragment-based screening approach to identify and develop small molecule compounds that bind to and inhibit the replication machinery or neuraminidase across different pandemic influenza strains and IAV strains with acquired resistance against commercial antivirals. While the influenza targets pursued in this project are well-established druggable anti-influenza targets, the novelty of the project is the focus on pandemic influenza strains, the use of the XCHEM platform to search for new chemical matter, and the access to state-of-the-art infrastructure such as the Diamond Light Source. The Oxford University based consortium undertaking this project consists of Professors; Thomas Bowden, Pramilla Rijal, Jonathan Grimes, Ervin Fodor, and Paul Brennan. Collectively an excellent team consisting of structural biologists, medicinal chemists, and virologists with in-depth knowledge of both targets and methodologies. The 3-year project will commence in the spring of 2024.