Matrine exhibits antiviral activities against PEDV by directly targeting Spike protein of the virus and inducing apoptosis via the MAPK signaling pathway.

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.

A new PEDV strain CH/HLJJS/2022 can challenge current detection methods and vaccines.

BACKGROUND: Porcine epidemic diarrhea virus (PEDV) variant strains cause great economic losses to the global swine industry. However, vaccines do not provide sufficient protection against currently circulating strains due to viral mutations. This study traced the molecular characteristics of the most recent isolates in China and aimed to provide a basis for the prevention and treatment of PEDV. METHODS: We obtained samples from a Chinese diarrheal swine farm in 2022. Reverse transcription polymerase chain reaction and immunofluorescence were used to determine the etiology, and the full-length PEDV genome was sequenced. Nucleotide similarity was calculated using MEGA to construct a phylogenetic tree and DNASTAR. Mutant amino acids were aligned using DNAMAN and modeled by SWISS-MODEL, Phyre2 and FirstGlance in JMOL for protein tertiary structure simulation. Additionally, TMHMM was used for protein function prediction. RESULTS: A PEDV virulent strain CH/HLJJS/2022 was successfully isolated in China. A genome-wide based phylogenetic analysis suggests that it belongs to the GII subtype, and 96.1-98.9% homology existed in the whole genomes of other strains. For the first time, simultaneous mutations of four amino acids were found in the highly conserved membrane (M) and nucleocapsid (N) proteins, as well as eight amino acid mutations that differed from the vast majority of strains in the spike (S) protein. Three of the mutations alter the S-protein spatial structure. In addition, typing markers exist during strain evolution, but isolates are using the fusion of specific amino acids from multiple variant strains to add additional features, as also demonstrated by protein alignments and 3D models of numerous subtype strains. CONCLUSION: The newly isolated prevalent strain CH/HLJJS/2022 belonged to the GII subtype, and thirteen mutations different from other strains were found, including mutations in the highly conserved m and N proteins, and in the S1° and COE neutralizing epitopes of the S protein. PEDV is breaking through original cognitions and moving on a more complex path. Surveillance for PEDV now and in the future and improvements derived from mutant strain vaccines are highly warranted.