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Coronavirus disease 2019 (COVID\u201019) caused by a novel severe acute respiratory syndrome CoV (SARS\u2010CoV\u20102) at the end of 2019 became a global pandemic. The 3C\u2010like cysteine protease (3CLpro) processes viral polyproteins to yield mature non\u2010structural proteins, thus playing an important role in the CoV life cycle, and therefore is considered as a prominent target for antiviral 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\u2010related SARS\u2010CoV, MERS\u2010CoV and SARS\u2010CoV\u20102, and explore the potency and mechanism of their cognate inhibitors. 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