Analyzing the potential therapeutic mechanism of Huashi Baidu Decoction on severe COVID-19 through integrating network pharmacological methods

Abstract

Background and aim: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods.

Experimental procedure: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected.

Results and conclusion: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19.

Taxonomy classification by evise: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.

Keywords: Active compounds; Anti-inflammation; Chinese materia medica; HSBD; Immune regulation.

Graphical abstract

Fig. 1

Venn diagram of the mapping the target proteins set of Huashi Baidu Decoction (HSBD) and the disease genes set of severe COVID-19.

Fig. 2

Protein-protein interaction (PPI) network diagram of potential therapeutic target proteins of Huashi Baidu Decoction on COVID-19. (A) The PPI network of 42 therapeutic target proteins of Huashi Baidu Decoction on severe COVID-19. The nodes indicate proteins, and edges represent protein-protein associations. (B) Clusters of the three main modules resolved from the PPI network by MCODE.

Fig. 3

GO_BiologicalProcess enrichment analysis of 45 potential therapeutic target proteins of Huashi Baidu Decoction on severe COVID-19. The bars show the percentage of genes in GO_BiologicalProcess terms.

Fig. 4

KEGG pathway enrichment analysis of 45 potential therapeutic target proteins of Huashi Baidu Decoction on severe COVID-19. The bars show the percentage of genes in KEGG pathway terms.

Fig. 5

The “Chinese materia medica-active compounds-therapeutic target proteins” network of Huashi Baidu Decoction on severe COVID-19. Diamond represents the potential therapeutic targets, circle represents the active compounds and square represents the Chinese materia medica. The larger the node, the more important it is. The edges represent the relationship between Chinese materia medica, active compounds and the potential therapeutic target proteins.