MERS-CoV RBD shares a structure similar to that of the homology domain of SARS-CoV (Wang et al., 2013). However, antibodies induced by SARS-CoV RBD have no cross-reactivity and/or cross-neutralizing activity to MERS-CoV (Du et al., 2013b). Moreover, MERS-CoV utilizes dipeptidyl peptidase 4 (DPP4) as a receptor through the RBD (CTD) region (Raj et al., 2013), which is distinct from the SARS-CoV receptor ACE2. Although the core regions of SARS-CoV and MERS-CoV RBDs are similar, their RBM regions are significantly different, which explains why they recognize different receptors (Li, 2015). MERS-CoV S trimer also maintains a structure similar to that of SARS-CoV S trimer. Both standing and lying states can be detected in the MERS-CoV RBDs, whereas DPP4 only binds to the standing RBD (Pallesen et al., 2017; Yuan et al., 2017). MERS-CoV is clustered with Ty-BatCoV HKU4 and Pi-BatCoV HKU5 in the subgenus Merbecovirus. Ty-BatCoV HKU4, but not Pi-BatCoV HKU5, could use human DPP4 as a receptor (Yang et al., 2014b). Recently, some MERS-related CoVs (MERSr-CoVs) have been discovered from bats that can enter human DPP4-expressing cells (Lau et al., 2018; Luo et al., 2018a). These findings suggest that the emergence of MERSr-CoV may threaten human health owing to their potential for cross-species transmission. The MERS-CoV S protein and RBD and their complexes, along with the DPP4 receptor, are shown in Supplementary Figures S1C,D.