Exploring the mechanism of quercetin treatment of bovine viral diarrhea mucosal disease based on network pharmacology and in vitro validation

Abstract

ABSTRACT: Bovine viral diarrhea virus (BVDV) can cause acute and persistent infections in cattle, resulting in significant economic losses to the livestock industry each year. Targeted antiviral therapy is an effective strategy. This study was based on network pharmacology, molecular docking techniques and in vitro studies to investigate quercetin’s mechanism in treating bovine viral diarrhea/mucosal disease (BVD-MD). The network topology analysis was carried out using Cytoscape 3.9.0 software to construct the network of “Chinese medicine ingredients-target-diseases”. Protein interactions were explored and analyzed using the String system (PPI). GO and KEGG pathway analysis of the intersected targets was performed using Bioconductor software. The molecular docking and molecular dynamics simulation methods were used to reveal the degree of binding of quercetin to key target genes. Western blot and indirect immunofluorescence were used to characterize the antiviral effects of quercetin. This study utilized network pharmacological analysis, identifying 22 targets associated with BVD-MD. The results of the KEGG pathway showed that quercetin was closely related to Ras and MAPK signaling pathways of BVD-MD. Molecular docking results showed that SRC, NS5B, NOX4 and XDH were the key targets of quercetin in the treatment of BVD-MD. Through network pharmacology, molecular docking and in vitro experiments, quercetin was demonstrated to combat bovine viral diarrhea mucosal disease through key targets of SRC, MAPK1, GSK3B, NS5B and E2. Molecular dynamics analysis showed that quercetin exhibited complex stability with NS5B. This study provides a theoretical and experimental basis for quercetin treatment of BVD-MD and later drug development.

Keywords

• BVD-MD
• quercetin
• web-based drug screening
• molecular docking
• antiviral