Characterization of host substrates of SARS-CoV-2 main protease

The main protease (M(pro)) plays a crucial role in coronavirus, as it cleaves viral polyproteins and host cellular proteins to ensure successful replication. In this review, we discuss the preference in the recognition sequence of M(pro) based on sequence-based studies and structural information and highlight the recent advances in computational and experimental approaches that have aided in discovering novel M(pro) substrates. In addition, we provide an overview of the current understanding of M(pro) host substrates and their implications for viral replication and pathogenesis. As M(pro) has emerged as a promising target for the development of antiviral drugs, further insight into its substrate specificity may contribute to the design of specific inhibitors.