Wogonin for COVID-19

Abstract Objective: Qu Du Qiang Fei 1 Hao Fang (QDQF1) is a novel Chinese herbal medicine formula used to treat coronavirus disease 2019 (COVID-19). However, the pharmacological mechanisms of action of QDQF1 remain unclear. The objective of this study was to identify the effective ingredients and biological targets of QDQF1 for COVID-19 treatment. Materials and Methods: The effective ingredients and mechanisms of action of QDQF1 were analyzed by using network pharmacology methods, which included an analysis of the effective ingredients and corresponding targets, COVID-19-related target acquisition, compound-target network analyses, protein-protein interaction network analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses, and molecular docking studies. Results: In total, 288 effective QDQF1 ingredients were identified. We identified 51 core targets from the 148 targets through an overlap between putative QDQF1 targets and COVID-19-related targets. Six key components, including formononetin, kaempferol, luteolin, naringenin, quercetin, and wogonin were identified through component-target network analyses. GO functional enrichment analysis of the core targets revealed 1296 items, while KEGG pathway enrichment analysis identified 148 signaling pathways. Nine central targets (CCL2, CXCL8, IL1B, IL6, MAPK1, MAPK3, MAPK8, STAT3, and TNF) related to the COVID-19 pathway were identified in the KEGG pathway enrichment analysis. Furthermore, molecular docking analysis suggested that the docking scores of the six key components to the nine central targets were better than those to remdesivir. Conclusions: QDQF1 may regulate multiple immune-and inflammation-related targets to inhibit the progression of severe acute respiratory syndrome coronavirus 2, and thus, may be suitable for the treatment of COVID-19.

Many inflammatory mechanisms are involved in the pathophysiology of COVID-19 infection. COVID-19 inhibits IFN antiviral responses, so we should expect an out-of-control viral replication. “Cytokine storms” occur due to the over-production of pro-inflammatory cytokines after an influx of neutrophils and monocytes/macrophages and may be responsible for the immunopathology of the lung involvement. Several cascades have been reported in the activation process of NF-κB. In this paper, to find new therapeutic options for COVID-19 infection, we reviewed some natural products that could potentially inhibit the NF-κB pathway. We found that sevoflurane, quercetin, resveratrol, curcumin, KIOM-C, bergenin, garcinia kola, shenfu, piperlongumine, wogonin, oroxylin, plantamajoside, naringin, ginseng, kaempferol, allium sativum L, illicium henryi, isoliquiritigenin, lianhua qingwen, magnoflorine, and ma Huang Tang might be effective in inhibiting the NF-KB pathway. These natural products could be helpful in the control of COVID-19 infections. However, larger clinical trials are needed to ascertain the efficacy of these products fully.

The current coronavirus disease 2019 (COVID-19) outbreak is alarmingly escalating and raises challenges in finding efficient compounds for treatment. Repurposing phytochemicals in herbs is an ideal and economical approach for screening potential herbal components against COVID-19. Andrographis paniculata, also known as Chuan Xin Lian, has traditionally been used as an anti-inflammatory and antibacterial herb for centuries and has recently been classified as a promising herbal remedy for adjuvant therapy in treating respiratory diseases. This study aimed to screen Chuan Xin Lian’s bioactive components and elicit the potential pharmacological mechanisms and plausible pathways for treating COVID-19 using network pharmacology combined with molecular docking. The results found terpenoid (andrographolide) and flavonoid (luteolin, quercetin, kaempferol, and wogonin) derivatives had remarkable potential against COVID-19 and sequelae owing to their high degrees in the component-target-pathway network and strong binding capacities in docking scores. In addition, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the PI3K-AKT signaling pathway might be the most vital molecular pathway in the pathophysiology of COVID-19 and long-term sequelae whereby therapeutic strategies can intervene.

The network pharmacological regulation mechanism has been studied in which Qing-Fei-Pai-Du Decoction (QFPDD) can be used for treating diabetic patients suffering from coronavirus disease 2019 (COVID-19). In this study, we retrieved the target genes of QFPDD along with its effective components from the Traditional Chinese medicine systems pharmacology database. The target genes of diabetes and COVID-19-associated diseases were searched based on the GeneCards database, and the co-target genes of QFPDD were obtained. The target genes were analyzed using the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes. Cytoscape software was used for constructing the “herb-ingredient-target” network. Then, the co-target genes were imported into the Metascape database to analyze protein–protein interaction. Based on the results of the analysis of the hub genes from each database, the key target genes and the active components of QFPDD effective for treating diabetic COVID-19 patients were obtained. The crystal structures of the key target genes were retrieved from the protein data bank database, and molecular docking (MD) was performed using the AutoDock Tool, PyMoL, Chen3D, and other software. In total, 305 active ingredients and 274 target genes were identified among 19 traditional Chinese medicines present in QFPDD. We found 4585 COVID-19 target genes, 16 660 diabetes target genes, and 60 drug-disease target genes. The results of the Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that the main function of these co-target genes was immune regulation. Additionally, protein interaction analysis and cluster analysis were performed to obtain a protein interaction network, and 3 core proteins and 4 core active components were found. According to the results of MD, the main effective components (quercetin, kaempferol, and wogonin) present in QFPDD were found to bind strongly to the receptor. The main active components of QFPDD were effective in treating diabetes complicated with COVID-19 through their actions on multiple biological pathways.