Recently, Qing et al. [113] demonstrated roles of S1A domains binding to Sia receptors and S1B domains binding to DDP4 receptors at different stages of virus infection. At the initial infection stage, MERS-CoV attaches to sialyl receptors on the host cell membrane and requires subsequent durable adherence to DDP4 receptors for infection. At later infection stages, MERS-CoV S proteins, which are not incorporated into progeny viruses, abundant on infected cell membranes attach to sialyl receptors on neighboring cells. This stage does not require DPP4 receptors but requires the cell surface protease TMPRSS2 for activating MERS-CoV S proteins for cell-cell fusions resulting in syncytial formation that rapidly spreads. These findings indicate the importance of Sia attachment playing roles in both initial and later infection stages and possibly determining the site of MERS-CoV infection since Sia attachment precedes DPP4 adherence at the initial infection stage.