PEDV is an enveloped, positive-sense, single-stranded RNA virus. The PEDV genome constitution represents a standard CoV arrangement. The viral genome is approximately 28 kb in length, containing a 5′ terminal cap, a 3′ poly (A) tail, as well as seven open reading frames (ORFs), including the ORF1a, ORF1b, S, ORF3, E, M, and N genes (Figure 1) [39,40,41]. The N terminal ORF1a and ORF1b encode two large replicase polyprotein precursors (pp1a and pp1ab), which are subsequently processed into 16 nonstructural proteins (nsp1 to 16). ORF1a encodes pp1a which is cleaved by viral proteases into 11 nonstructural proteins (nsp1-nsp11). The ORF1b generates five additional nonstructural proteins (nsp12–16) that are proteolytically cleaved by the viral proteases from pp1ab [42]. Nsp3 contains two papain-like protease domains (PLP1 and PLP2 or PLpro) that cleave the nsp1–4 region of the replicase polyprotein at three sites. Nsp5, a chymotrypsin-like enzyme also known as 3C-like protease, cleaves the polyprotein at remaining cleavage sites [43]. The C terminus of viral genome contains five ORFs, encoding four structure proteins (spike protein (S), small envelope glycoprotein (E), membrane glycoprotein (M), and nucleocapsid protein (N)), as well as a hypothetical accessory protein ORF3 [44,45,46]. The 16 nsps, together with the N protein, and several host proteins, form a large replication and transcription complex (RTC) that engages in the minus-strand RNA synthesis, using viral genomic RNA. These nsps play important roles in virion structure modification and the replication and transcription of PEDV [47].