Network pharmacology and molecular docking analysis on molecular targets and mechanisms of Huashi Baidu formula in the treatment of COVID-19.
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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.
SUBMITTER: Tao Q
PROVIDER: S-EPMC7441778 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Traditional Chinese medicine (TCM) has exerted positive effects in controlling the COVID-19 pandemic. HuaShi XuanFei Formula (HSXFF) was developed to treat patients with mild and general COVID-19 in Zhejiang Province, China. The present study seeks to explore its potentially active compounds and pharmacological mechanisms against COVID-19 based on network pharmacology, molecular docking, and molecular dynamics (MD) simulation. All components of HSXFF were harvested from the pharmacology database of the TCMSP system. COVID-19-related targets were retrieved from using OMIM and GeneCards databases. The herb-compound-targets network was constructed by Cytoscape. The target protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to discover the potential key target genes and mechanism. The main active compounds of HSXFF were docked with 3C-like (3CL) protease hydrolase and angiotensin-converting enzyme 2 (ACE2). The MD simulation confirmed the binding stability of docking results. The herbs-targets network mainly contained 52 compounds and 70 corresponding targets, including key targets such as RELA, TNF, TP53, IL6, MAPK1, CXCL8, IL-1β, and MAPK14. The GO and KEGG indicated that HSXFF may be mainly acting on the IL-17 signaling pathway, TNF signaling pathway, NF-κB signaling pathway, etc. The molecular docking results indicated that isovitexin and procyanidin B1 showed the highest affinity with 3CL and ACE2, respectively, which were confirmed by MD simulation. These findings suggested HSXFF exerted therapeutic effects involving "multi-compounds and multi-targets." It might be working through directly inhibiting the virus, improving immune function, and reducing the inflammatory in response to anti-COVID-19. In summary, the present study would provide a valuable direction for further research of HSXFF.
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