The coronavirus spike protein and the influenza virus hemagglutinin are class I viral membrane fusion proteins. While the two proteins display strong structural conservation and the mechanisms underlying membrane fusion are similar, they share no sequence similarity. Whether they are functionally interchangeable is currently unknown. In this study, we constructed scIAV-S, a single-cycle influenza A virus pseudotyped with the spike protein of porcine epidemic diarrhea virus (PEDV), and demonstrated that this virus could infect cultured cells and trigger massive syncytium formation. Treatment with endocytosis inhibitors did not affect syncytium formation by infected cells. Moreover, the infectivity of scIAV-S was associated with the degree of cell adaptation of PEDV-S. Intriguingly, scIAV-S lacking functional neuraminidase (NA) exhibited substantially higher infectivity, suggesting a pivotal role of the sialic acid in the binding/entry of PEDV. Together, scIAV-S offers a robust platform for the investigation of the entry mechanism of PEDV or, possibly, of other coronaviruses.