Exploration on the potential mechanism of baicalein on Porcine Deltacoronavirus infection based on network pharmacology

ABSTRACT

This study aimed to explore the protective mechanism of baicalein against porcine deltacoronavirus (PDCoV) infection. The targets of baicalein were obtained through Pharmamapper, Pubchem, STITCH, TCMSP and Swiss Targer Prediction databases, and the targets of PDCoV infection were obtained according to the proteomics data from our previous study. The targets of baicalein-PDCoV interaction were obtained and analyzed by STRING database and Cytoscape 3.8.2 software to construct a network diagram of "baicalein-PDCoV-targets". The CytoNCA was used to analyze network topology and core network construction. Metascape database was used for GO and KEGG analysis of core network genes. The expression levels of genes in the predicted signaling pathways were detected in vitro. A total of 268 potential targets of baicalein were screened out. There were 75 potential targets of baicalein-PDCoV infection. GO enrichment results showed that baicalein was mainly involved in the formations of membrane raft, spindle and mitochondrial membrane, cell cycle and MAPK signaling pathways. A total of 277 signaling pathways (P < 0.01) were screened out by KEGG enrichment. The PI3K-Akt, Ras and MAPK signaling pathways were the main pathways that involved in the protective effects of baicalein against PDCoV infection. The results showed that compared with the cellular control groups, the mRNA expressions of PI3K, AKT and NF-B significantly increased in the PDCoV infection group. Compared with the PDCoV group, treatment of baicalein significantly decreased the mRNA expressions of PI3K, AKT and NF-B (P < 0.05). The effect of baicalein on PDCoV infection has the characteristics of multi-targets and multi-pathways, through the intervention of AKT1, HSP90AA1, SRC, EGFR, CASP3, MAPK, STAT3 and other core genes in regulating PI3K-Akt signaling pathway, Ras signaling pathway and MAPK signaling pathway, apoptosis, and virus infection. These results suggested that baicalein could be a potential therapeutic drug against PDCoV infection for further study.