Abstract
The three-year COVID-19 pandemic 'has' caused a wide range of medical, social, political, and financial implications. Since the end of 2020, various mutations and variations in SARS-CoV-2 strains, along with the immune escape phenomenon, have emerged. There is an urgent need to identify a relatively stable target for the development of universal vaccines and drugs that can effectively combat both SARS-CoV-2 strains and their mutants. Currently, the main focus in treating SARS-CoV-2 lies in disrupting the virus's life cycle. The main protease (M(pro)) is closely associated with virus replication and maturation and plays a crucial role in the early stages of infection. Consequently, it has become an important target for the development of SARS-CoV-2-specific drugs. This review summarizes the recent research progress on the novel coronavirus's main proteases, including the pivotal role of M(pro) in the virus's life cycle, the structure and catalytic mechanism of M(pro), the self-maturation mechanism of M(pro), the role of M(pro) in virus immune escape, the current methods of developing antiviral drugs targeting M(pro), and the key drugs that have successfully entered clinical trials. The aim is to provide researchers involved in the development of antiviral drugs targeting M(pro) with systematic and comprehensive information.