In silico analysis of the potential mechanism of a preventive Chinese medicine formula on coronavirus disease 2019

Abstract

Ethnopharmacological relevance With the spread of Coronavirus Disease (2019) (COVID-19), combination with traditional Chinese medicine (TCM) has been widely used as a prevention and therapy strategy in China. Xin guan No.1 (XG-1) prescription is a preventive formula recommended by the Hunan Provincial Administration of TCM to prevent the pandemic of COVID-19. Aim of the study To explore the potential preventive mechanisms of XG-1 against COVID-19 in the combination of network pharmacology approach, single-cell RNA expression profiling analysis, molecular docking and retrospective study. Materials and methods Encyclopedia of Traditional Chinese Medicine (ETCM) database was used to determine the meridian tropism, active components and target genes of XG-1. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis were conducted by R Cluster Profiler package (3.14.3). Single cell RNA sequencing (scRNA-seq) data of human lung (GSE122960) was downloaded from Gene Expression Omnibus (GEO) database and analyzed by R Seurat package (3.1.2). Cytoscape (3.7.2) was used to construct the interaction network. The main ingredients in XG-1 were identified by HPLC- Q-TOF- MS and used for molecular docking with COVID-19 3CL hydrolytic enzyme and angiotensin converting enzyme II (ACE2). A retrospective study of 47 close contact participants from Dongtang Community of Hunan Province was conducted to evaluated the preventive effect of XG-1. Results According to the network pharmacology analysis, XG-1 formula was closely related to lung-, spleen- and stomach-meridians and include a total of 206 active components and 853 target genes. GO and KEGG pathway enrichment revealed that XG-1 mainly regulated cellular amino acid metabolism process and neuroactive ligand-receptors interaction. The scRNA-seq profiling showed that angiotensin converting enzyme 2 (ACE2) was principally expressed in alveolar type 2 epithelial cells (AT2). 153 genes were up-regulated in AT2 cells expressing ACE2 and 12 genes were obtained by intersecting with XG-1 target genes, of which 3 were related to immunity. Five main chemical ingredients were detected in XG-1 sample by HPLC-Q-TOF-MS. The molecular docking showed that Rutin, Liquiritin and Astragaloside Ⅳ had a good affinity with COVID-19 3CL hydrolytic enzyme and ACE2. Compared with participants who didn't take XG-1, preventive treatment with XG-1gradules resulted in a significant lower rate of testing positive for SARS-CoV-2 nucleic acid (P < 0.0001). Conclusion The present study showed that XG-1 exerts a preventive effect in close contacts against COVID-19. The underlying mechanism may be related to modulate immunity response through multiple components, pathways, and several target genes co-expressed with ACE2. These findings provide preliminary evidences and methodological reference for the potential preventive mechanism of...

Chemical Composition of Honeysuckle (Lonicerae japonicae) Extracts and Their Potential in Inhibiting the SARS-CoV-2 Spike Protein and ACE2 Binding, Suppressing ACE2, and Scavenging Radicals

“…Typical flavonoids including quercetin and luteolin were found in honeysuckle extracts (Table ). The existence of these compounds and the effects of honeysuckle extracts in inhibiting the interaction between the spike protein of SARS-CoV-2 and ACE2 could be supported by previous computational molecular docking studies that suggest these bioactive flavonoids might have potential COVID-19 related inhibition . In addition, other extracts of botanical herbs, such as the ethanol and water extracts of cloves, were shown to inhibit the binding between the SARS-CoV-2 spike protein and ACE2, which is consistent with our observations in the present study. , These observations indicated that honeysuckle extracts, especially the ethanol extract, might show remarkable anti-COVID-19 effects by blocking the interaction between the SARS-CoV-2 spike protein and ACE2.…”

“…The relative ion intensity of each identified compound is shown in Table 1. Sesamoside (6), loganic acid (8), secologanic acid (9), 4-caffeoylquinic acid (10) and kaempferol (27) were the five major compounds in the water extract (Table 1), whereas luteolin (28), colossolactone E (31), salvigenin (32), atractylon (35) and zerumbone (36) were the major compounds in the ethanol extract (Table 1). 3-Caffeoylquinic acid (7) and capparoside A (15) were the two major compounds in both water and ethanol extracts.…”

“…The difference in water and ethanol extracts may be attributed to the chemical profile differences. The major chemicals identified in the water extract were sesamoside (6), loganic acid (8), secologanic acid (9), 4caffeoylquinic acid (10) and kaempferol (27) while the major chemicals identified in the ethanol extract were luteolin (28), colossolactone E (31), salvigenin (32), atractylon (35) and zerumbone (36) (Table 1). A plausible explanation is that the major chemicals in the water extract had higher free radical scavenging capacities and the interaction of the chemicals may modify the scavenging capacities in both extracts.…”

Promising natural products against SARS‐CoV‐2: Structure, function, and clinical trials

“…The structure of rutinum is shown in Figure 4d . In China’s drug intervention program against COVID‐19, prescription XG‐1 has shown good treatment effects (Wu et al, 2021 ). By conducting pharmacological network construction and molecular docking experiments on XG‐1, Wu et al screened out rutinum as one of the high‐efficiency targets (Wu et al, 2021 ), which docked to ACE2 and 3CLpro (Wu et al, 2021 ).…”

“…In China’s drug intervention program against COVID‐19, prescription XG‐1 has shown good treatment effects (Wu et al, 2021 ). By conducting pharmacological network construction and molecular docking experiments on XG‐1, Wu et al screened out rutinum as one of the high‐efficiency targets (Wu et al, 2021 ), which docked to ACE2 and 3CLpro (Wu et al, 2021 ). Tien’s group designed a more hydrophobic analog of rutin (Rutin‐M) to enhance its target ability to 3CLpro in an aqueous solution (Huynh, Wang, Cornell, & Luan, 2020 ).…”