The pharmacological mechanism of Huashi Baidu Formula for the treatment of COVID-19 by combined network pharmacology and molecular docking

Abstract

Background: Huashi Baidu Formula (HSBDF) is a traditional Chinese medicine formula consisting of fourteen parts, which has been proven effective for treating coronavirus disease 2019 (COVID-19) clinically.However, the therapeutic mechanism of the effect of HSBDF on COVID-19 remains unclear.Methods: The components and action targets of HSBDF were searched in the TCMSP, YaTCM, PubChem, and TargetNet databases. Disease targets related to ACE2 were screened in single-cell sequence data of colon epithelial cells from other reports. The therapeutic targets of HSBDF for COVID-19 were obtained by integrated analysis, and the protein-protein interaction was analyzed using the STRING database. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) processes were analyzed using the OmicsBean and Metascape databases. The communication between networks [component-target (C-T) network, component-target-pathway (C-T-P) network, herb-target (H-T) network, target-pathway (T-P) network, and meridian-tropism (M-T) network] was constructed by Cytoscape software. The Cloud computing molecular docking platform was used to verify the molecular docking.Results: The obtained 223 active ingredients and 358 targets of HSBDF. The 5,555 COVID-19 disease targets related to ACE2 were extracted, and 84 compound-disease common targets were found, of which the principal targets included ACE, ESR1, ADRA1A, and HDAC1. A total of 3,946 items were seized by GO enrichment analysis, mainly related to metabolism, protein binding, cellular response to the stimulus, and receptor activity. The enriched KEGG pathways screened 46 signaling pathways, including the reninangiotensin system, the renin secretion, NF-kappa B pathway, the arachidonic acid metabolism, and the AMPK signaling pathway. The molecular docking results showed that the bioactive components of HSBDF have an excellent binding ability with main proteins related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Conclusions: HSBDF might act on SARS-CoV-2 through multiple components, targets, and pathways.Here we reveal preliminary results of the mechanism of action of HSBDF on SARS-CoV-2, providing a theoretical basis for future clinical applications.

Machine Learning Applications in Drug Repurposing

“…Computational method-assisted drug design is mainly by employing approaches of molecular docking and network pharmacology. To date, there have a considerable volume of works focused on developing methods of network pharmacology and molecular docking based on traditional Chinese medicine (TCM) to fight against COVID-19 [10,11]. The results indicate that TCM compounds can play an indirect therapeutic effect by directly acting on the new coronavirus or by anti-inflammatory and immune regulation.…”

Therapeutic mechanisms and impact of traditional Chinese medicine on COVID-19 and other influenza diseases

“…DC. ), Caoguo (Amomum Tsaoko: Chinese Cardamom Seeds), Shenghuangqi (Hedysarum Multijugum Maxim: Astragalus Carthamus) [ 25 , 98 ].…”

“…Network pharmacology and molecular docking revealed targets ACE2, ADRA1A, ESR1, and HDAC1 for key components in HSBD. The enriched KEGG analysis screened vital signaling pathways, renin-angiotensin and secretion, NF-kB, AMP-activated protein kinase, and arachidonic acid metabolism in COVID-19 patients after treatment [98] , revealing that HSBD may inhibit SARS-CoV-2 via multiple sites and pathways. Modulations of signaling pathways, such as AGE-RAGE, NF-kB, RIG-I-like receptor, and TNFα, might mediate HSBD therapeutic effects on severe COVID-19 patients [100] .…”

Updated pharmacological effects of Lonicerae japonicae flos, with a focus on its potential efficacy on coronavirus disease–2019 (COVID-19)

“…Of these 20 postulated targets of LJF, the heat shock protein family B (small) member 1 [ 35 ], plasminogen activator, urokinase [ 36 ], interleukin 6 receptor [ 37 ], TNF [ 38 ], myeloperoxidase [ 39 ], estrogen receptor 1 [ 40 ], IL6 [ 41 ], heme oxygenase 1 [ 42 ], IL10 [ 43 ], epidermal growth factor receptor [ 44 ], nitric oxide synthase 3 [ 45 ], and albumin [ 46 ] have been validated to be highly correlated with the initiation and development of COVID-19, and these target genes of LJF are implicated in the inflammatory reaction, oxidative stress, immune regulation, and respiratory function, implying the actions of LJF on these multiple targets orchestrate its efficacy on COVID-19.…”