ABSTRACT
BACKGROUND: Huangqi with the capacity to resist virus and preserve myocardium is a potential herb for treating patients with COVID-19 and related myocardial injury. METHOD: We applied network pharmacology method and programming software including R and Perl to explore the probable mechanism of Huangqi fighting against the disease. Ingredients and target gene names of Huangqi were obtained from TCMSP database. Disease-associated genes were mined by searching GeneCards database. Venny online software was applied to draw Venn diagram of intersection genes. Cytoscape software was used to set up the network of disease, drug, compounds and targets. STRING database was applied to set up protein protein interaction (PPI) network. With intersection genes imported into WEBGESALT database, gene ontology (GO) analysis was completed. An R script basing on Kyoto Encyclopedia of Genes and Genomes (KEGG) database was applied to obtain KEGG pathways. Finally, we used AutoDockTools 1.5.6 software for molecular docking and PyMOL to visualize the docking details. RESULTS: We obtained 20 active components and 18 potential target genes to construct a network, and found out quercetin and kaempferol were core ingredients. Key targets included EGFR, MAPK8, IL6, CASP3, RELA and PPARG. Huangqi showed its potential to can reduce inflammatory response to prevent cytokine storm by inhibiting EGFR, IL6 and MAPK and protect myocardium by inhibiting apoptosis and oxidant stress. Huangqi may also work by adjusting ubiquitin and regulating multiple viral pathways. CONCLUSIONS: Huangqi may play a therapeutic role in treating COVID-19 with myocardial injury by the effects of resisting virus and protecting myocardium concurrently.
ABSTRACT
COVID-19 is threatening human health worldwide but no effective treatment currently exists for this disease. Current therapeutic strategies focus on the inhibition of viral replication or using anti-inflammatory/immunomodulatory compounds to improve host immunity, but not both. Traditional Chinese medicine (TCM) compounds could be promising candidates due to their safety and minimal toxicity. In this study, we have developed a novel in silico bioinformatics workflow that integrates multiple databases to predict the use of honeysuckle (Lonicera japonica) and Huangqi (Astragalus membranaceus) as potential anti-SARS-CoV-2 agents. Using extracts from honeysuckle and Huangqi, these two herbs upregulated a group of microRNAs including let-7a, miR-148b, and miR-146a, which are critical to reduce the pathogenesis of SARS-CoV-2. Moreover, these herbs suppressed pro-inflammatory cytokines including IL-6 or TNF-α, which were both identified in the cytokine storm of acute respiratory distress syndrome, a major cause of COVID-19 death. Furthermore, both herbs partially inhibited the fusion of SARS-CoV-2 spike protein-transfected BHK-21 cells with the human lung cancer cell line Calu-3 that was expressing ACE2 receptors. These herbs inhibited SARS-CoV-2 Mpro activity, thereby alleviating viral entry as well as replication. In conclusion, our findings demonstrate that honeysuckle and Huangqi have the potential to be used as an inhibitor of SARS-CoV-2 virus entry that warrants further in vivo analysis and functional assessment of miRNAs to confirm their clinical importance. This fast-screening platform can also be applied to other drug discovery studies for other infectious diseases.