Molecular insight into the therapeutic promise of xuebijing injection against coronavirus disease 2019

ABSTRACT

Background: The potential human-to-human transmission of the coronavirus pneumonia (coronavirus disease 2019 [COVID-19]) has caused an outbreak of acute respiratory illness. Xuebijing injection is recommended as first-line treatment for the severe and critical patients with COVID-19. The aim of present study is to interpret the pharmacological mechanisms and molecular connections of Xuebijing injection against COVID-19 by utilizing the approaches of network pharmacology and molecular docking. Materials and Methods: Active ingredients of Xuebijing injection were collected by Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and putative therapeutic targets were screened from TCMSP, SwissTargetPrediction, and STITCH databases. Moreover, the protein-protein interactions, topological analysis, and pathway enrichment were established to distinguish the hub targets and pathways by employing STRING database, Cytoscape software, DAVID database, respectively. In addition, the potential interaction and binding activity of candidate ingredients in Xuebijing injection with core targets were revealed by molecular docking simulation (AutoDock software). Results: A total of 115 bioactive components in Xuebijing injection were collected, and416 targets including AKT1, TP53, VEGFA, ALB, TNF and so on were responsible for treating COVID-19. Bioinformatics analysis revealed that matching core targets were closely associated with the inhibition of cytokine storm for its clinical beneficial effects in severe cases. The results of enrichment analysis indicated that PI3K-Akt signaling pathway, human T-cell leukemia virus type 1 infection, mitogen-activated protein kinase signaling pathway, tuberculosis, focal adhesion, TNF signaling pathway, and small-cell lung cancer were represented pathways of Xuebijing injection against COVID-19 in terms of lung inflammation, virus infection, and lung injury. Meanwhile, the active ingredients of Xuebijing injection exerted superior binding activities with 3CLpro and angiotensin-converting enzyme 2 as observed via molecular docking simulation. Conclusions: Through the comprehensive analysis of network pharmacology, the current research preliminarily elaborated the molecular regulation of therapeutic mechanisms for Xuebijing injection against COVID-19 and binding activity between active components and core targets, which provided scientific evidence to facilitate the development of Xuebijing injection and clinical treatment for COVID-19.