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

Wen-Ting Qiao; Xin Yao; Wei-Hong Lu; Yu-Qian Zhang; Kanwar Kumar Malhi; Hui-Xin Li; Jin-Long Li

doi:10.1016/j.ijbiomac.2024.132408

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

Int J Biol Macromol. 2024 May 14;270(Pt 2):132408. doi: 10.1016/j.ijbiomac.2024.132408. Online ahead of print.

Authors

Wen-Ting Qiao¹, Xin Yao¹, Wei-Hong Lu¹, Yu-Qian Zhang¹, Kanwar Kumar Malhi¹, Hui-Xin Li², Jin-Long Li³

Affiliations

¹ College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China.
² State Key Laboratory for Animal Disease Control and Prevention, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, PR China. Electronic address: lihuixin@caas.cn.
³ College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, PR China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, PR China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, PR China. Electronic address: Jinlongli@neau.edu.cn.

PMID: 38754683
DOI: 10.1016/j.ijbiomac.2024.132408

Abstract

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.

Keywords: Antiviral drugs; Matrine; PEDV.