Structural biology of SARS-CoV-1/SARS-CoV-2 main protease

The SARS-CoV-1/SARS-CoV-2 main protease cleaves the nascent viral polyproteins into biologically functional molecules, which are essential for viral reproduction inside the host cell. With more than 500 crystal structures available, it is one of the most heavily researched coronavirus proteins and a popular drug target. This review focuses on putting the function and structure of the main protease into a historical perspective, highlighting the structure-based design of inhibitors of the main protease and discussing potential future research directions.