Genetic Epidemiology of Porcine Epidemic Diarrhea Virus Circulating in China From 2010 to 2024: Characterization of Phylogenetic and Genetic Diversity of S1-Based Genes

As a porcine alphacoronavirus, porcine epidemic diarrhea virus (PEDV) frequently undergoes mutations that significantly reduce the effectiveness of current prevention and control strategies, leading to recurrent outbreaks in China. This study investigates the genetic evolution and mutation patterns of the S1 protein to characterize PEDV variation in China. Genetic evolutionary analysis of 804 PEDV S1 genes, including 620 Chinese PEDV strains, revealed that 78.06% of the Chinese PEDV strains belong to the G2a-subgroup, further divided into seven branches (G2a-Clade 1–7), with the predominant strains from 2020 to 2024 being in G2a-Clade 4 (68.00%). From 2021 to 2024, 32 novel substitutions, 25 deletions, and 8 insertions were identified in the S1 protein of Chinese strains compared to those from 2010 to 2011. Notably, complete mutations were observed at amino acid sites N139D, H189Y, L229P, I287M, F345L, A361T, T499I, and A520S. Moreover, protein homology modeling analysis displayed that these deletion–insertion mutations significantly altered the surface structure of the S protein, particularly in the N-terminal domain (NTD) and receptor-binding domain (RBD) regions of S1 protein. The predictive analysis using AlphaFold3 indicated that deletion–insertion mutations in the S1-RBD region notably affected the binding affinity of the S protein to porcine DC-SIGN. These findings enhance our understanding of the genetic evolution of PEDV in China.