Coronaviruses (CoVs) are positive single-stranded RNA viruses that cause severe respiratory syndromes in humans, including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). Coronavirus Disease 2019 (COVID-19) caused by a novel Severe Acute Respiratory Syndrome CoV (SARS-CoV-2) at the end of 2019 became a global pandemic . The 3C-like cysteine protease (3CLpro) process viral polyproteins to yield mature non-structural proteins, thus playing an important role in the CoV life cycle and therefore is considered a prominent target for anti-viral drugs . To date, many 3CLpro inhibitors have been reported, and their molecular mechanisms have been illustrated . Here, we briefly introduce the structural features of 3CLpro of the human-related SARS-CoV, MERS-CoV and SARS-CoV-2, and explore the potency and mechanism of their cognate inhibitors . This information will shed light on the development and optimization of CoV 3CLpro inhibitors, which may benefit further designation of therapeutic strategies to treat CoV diseases.