The subfamily Coronavirinae contains over 30 species of coronaviruses (CoVs).They can infect mice,rats,chickens,turkeys,swine,dogs,cats,rabbits,horses,cattle and so on,resulting in considerable economic losses worldwide.CoV Main protease (Mpro),which plays a pivotal role in viral replication and transcription through a highly complex cascade of processing,was identified as an ideal target for drug design.After solving a series of structures of CoV main proteases and enzyme-substrate complexes,we discovered that a region of the substrate-binding pocket from all CoVs is highly conserved across species.