CoV S proteins are typical class I viral fusion proteins, and protease cleavage is required for activation of the fusion potential of S protein23. A two-step sequential protease cleavage model has been proposed for activation of S proteins of SARS-CoV and MERS-CoV24,25, priming cleavage between S1 and S2 and activating cleavage on S2’ site. Depending on virus strains and cell types, CoV S proteins may be cleaved by one or several host proteases, including furin, trypsin, cathepsins, transmembrane protease serine protease-2 (TMPRSS-2), TMPRSS-4, or human airway trypsin-like protease (HAT)25–32. Availability of these proteases on target cells largely determines whether CoVs enter cells through plasma membrane or endocytosis. However, whether any of these proteases could promote virus entry of SARS-CoV-2 remains elusive.