Material Basis and Mechanism of Chansu Injection for COVID-19 Treatment Based on Network Pharmacology and Molecular Docking Technology

Abstract

Background: Coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving disease with no effective drug treatment. Traditional Chinese medicines have been widely used to treat COVID-19 in China. Chansu and its major active constituent, bufalin, exert broad-spectrum antiviral effects. Although the clinical efficacy of Chansu injection for COVID-19 treatment has been confirmed, its mechanism of action remains unclear. Objectives: In this study, we used network pharmacology and molecular docking technology to explore the potential material basis and mechanism of action of Chansu injection for COVID-19 treatment. Methods: The main components of Chansu injection were determined using high-performance liquid chromatography (HPLC). The PharmMapper, SwissTargetPrediction, SEA, and TCMID databases were used to screen for the active ingredients and therapeutic targets of Chansu injection while the OMIM and GeneCards Suite databases were used to search for COVID-19-related targets. The STRING database was used for protein–protein interaction (PPI) network construction and topological analysis while DAVID was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the core targets. Molecular docking of the three Chansu injection components (i.e., cinobufagin, resibufogenin, and bufalin) to angiotensin-converting enzyme II, spike (S) protein, 3CL protease, and RNA-dependent RNA polymerase was also carried out. Results: The three Chansu injection compounds were identified using HPLC. A total of 236 drug-related targets and 16,611 disease-related targets were identified, and 77 common targets were determined through mapping. The PPI mapping results revealed 16 core targets obtained through topological analysis and screening. Further, GO and KEGG pathway enrichment analyses revealed that the PI3K and JAK–STAT signaling pathways are the major pathways regulated by Chansu injection in COVID-19 treatment. The molecular docking results suggest that the three Chansu injection components have high binding energies to the S protein. Conclusions: This study revealed that the potential mechanism of Chansu injection for COVID-19 treatment involves multiple targets and pathways, thereby providing a scientific basis for its clinical application and further research.