Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19

Drug Dev Ind Pharm. 2020 Aug;46(8):1345-1353. doi: 10.1080/03639045.2020.1788070. Epub 2020 Jul 8.

Abstract

Purpose: Huashi Baidu formula (HSBDF) was developed to treat the patients with severe COVID-19 in China. The purpose of this study was to explore its active compounds and demonstrate its mechanisms against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through network pharmacology and molecular docking.

Methods: All the components of HSBDF were retrieved from the pharmacology database of TCM system. The genes corresponding to the targets were retrieved using UniProt and GeneCards database. The herb-compound-target network was constructed by Cytoscape. The target protein-protein interaction network was built using STRING database. The core targets of HSBDF were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The main active compounds of HSBDF were docked with SARS-CoV-2 and angiotensin converting enzyme II (ACE2).

Results: Compound-target network mainly contained 178 compounds and 272 corresponding targets. Key targets contained MAPK3, MAPK8, TP53, CASP3, IL6, TNF, MAPK1, CCL2, PTGS2, etc. There were 522 GO items in GO enrichment analysis (p < .05) and 168 signaling pathways (p < .05) in KEGG, mainly including TNF signaling pathway, PI3K-Akt signaling pathway, NOD-like receptor signaling pathway, MAPK signaling pathway, and HIF-1 signaling pathway. The results of molecular docking showed that baicalein and quercetin were the top two compounds of HSBDF, which had high affinity with ACE2.

Conclusion: Baicalein and quercetin in HSBDF may regulate multiple signaling pathways through ACE2, which might play a therapeutic role on COVID-19.

Keywords: Huashi Baidu formula; SARS-CoV-2; coronavirus; molecular docking; network pharmacology.

MeSH terms

  • Angiotensin-Converting Enzyme 2
  • Betacoronavirus / chemistry
  • Betacoronavirus / drug effects*
  • Betacoronavirus / genetics
  • COVID-19
  • COVID-19 Drug Treatment
  • China
  • Coronavirus Infections / drug therapy*
  • Databases, Factual
  • Drugs, Chinese Herbal / pharmacology*
  • Drugs, Chinese Herbal / therapeutic use*
  • Gene Ontology
  • Gene Targeting
  • Genes, Viral / drug effects
  • Genes, Viral / genetics
  • Humans
  • Medicine, Chinese Traditional
  • Molecular Docking Simulation / methods*
  • Pandemics
  • Peptidyl-Dipeptidase A / drug effects
  • Peptidyl-Dipeptidase A / genetics
  • Pharmacology, Clinical / methods*
  • Pneumonia, Viral / drug therapy*
  • SARS-CoV-2
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Drugs, Chinese Herbal
  • huashi baidu
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Grant support

This study was funded by the National Natural Science Foundation of China [Grant no. 81403296], the Natural Science Foundation of Guangdong Province [Grant no. 2017A030313827], and Science Program for Overseas Scholar (Xinhuo plan) of Guangzhou University of Chinese Medicine.