A Chemical Strategy for the Degradation of the Main Protease of SARS-CoV‑2 in Cells

SARS-CoV-2 is the virus that causes the global pandemic of COVID-19. The main protease (M^pro) of SARS-CoV-2 is essential for viral infection and is one of the major therapeutic targets for COVID-19. Here, we report the design, synthesis, and biological characterization of a novel heterobifunctional small molecule that could effectively induce the degradation of SARS-CoV-2 M^pro and its drug-resistant mutants in HEK 293T cells, thus demonstrating a new alternative strategy for intervening with proteins important for this novel coronavirus.