The complete genome of PEDV is approximately 28 kilobase pairs and consists of seven open reading frames (ORF). Out of the seven, four ORFs are responsible for encoding structural proteins, namely the spike (S) glycoprotein as well as envelop (E), membrane (M), and nucleocapsid (N) proteins, which are crucial for viral morphogenesis and establishment of infection establishment [7]. Among all coronaviruses, S glycoprotein plays a particularly essential role in cell-virus interaction and acts as the vital determinants of viral virulence/attenuation [8,9,10]. S glycoprotein is a homotrimeric type I fusion protein, which can be cleaved into two parts—the S1 and S2 subunits—by cellular protease [11]. The S1 subunit contains the receptor binding domain (RBD) and several neutralizing epitopes that are essential for determining host and tissue tropism, and triggering protective host immunity, respectively. Therefore, the S1 subunit has long been considered to be the primary target for vaccine development. The S2 domain, on the other hand, mediates membrane fusion which facilitates release of viral RNA and infection to the neighboring cells [8].