The unprecedented COVID-19 pandemic is threatening global health. It is unclear if and when a vaccine will become available. This project aims to advance the development of specific antiviral drugs targeting SARS-CoV-2 infections. The replication cycle of SARS-CoV-2 in the human host cell has one Achilles heel, the viral main protease. However, most main protease inhibitors reported to date have limited prospects as drug candidates. We have established a main protease inhibition assay in our laboratory, allowing us to identify new drug candidates. This project will design, synthesise and evaluate a series of small molecules as new lead compounds against SARS-CoV-2. You will explore “warheads” such as alpha-ketoamides and Michael acceptors to inactivate the SARS-CoV-2 main protease by covalent modification of its active site.