Structural biology of SARS-CoV-2 Mpro and drug discovery

Since its outbreak in late 2019, the COVID-19 pandemic has drawn enormous attention worldwide as a consequence of being the most disastrous infectious disease in the past century. As one of the most immediately druggable targets of SARS-CoV-2, the main protease (Mpro) has been studied thoroughly. In this review, we provide a comprehensive summary of recent advances in structural studies of Mpro, which provide new knowledge about Mpro in terms of its biological function, structural characteristics, substrate specificity, and autocleavage process. We examine the remarkable strides made in targeting Mpro for drug discovery during the pandemic. We summarize insights into the current understanding of the structural features of Mpro and the discovery of existing Mprotargeting drugs, illuminating pathways for the future development of anti-SARS-CoV-2 therapeutics.