Similar to HCoV-NL63 (Hofmann et al., 2005; Li, 2015), SARS-CoV recognizes, through the RBD in the CTD region of its S1 subunit, angiotensin-converting enzyme 2 (ACE2) as the receptor on the target cell (Li et al., 2003). The RBD (CTD) in two states (standing or lying) has been observed in the trimeric S protein. ACE2 binds to standing RBD, specifically in the receptor-binding motif (RBM), keeping the RBD in the “standing” state (Yuan et al., 2017). In addition to human ACE2, SARS-CoV S protein could also bind to palm civet and mouse ACE2s (Li et al., 2004; Li, 2008). Mutations in the RBD of S1 subunit are required for cross-species transmission of SARS-CoV (Li et al., 2005c; Li, 2008, 2016). Several bat SARSr-CoVs have been identified, and these CoVs can utilize human ACE2 as their receptor to bind the target cells (Ge et al., 2013; Hu et al., 2017). The structure of SARS-CoV S trimer and RBD binding to the ACE2 receptor is shown in Supplementary Figures S1A,B.