Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway

Ma, Qiang; Li, Runfeng; Pan, Weiqi; Huang, Wenbo; Liu, Bin; Xie, Yuqi; Wang, Zhoulang; Li, Chufang; Jiang, Haiming; Huang, Jicheng; Shi, Yongxia; Dai, Jun; Zheng, Kui; Li, Xiaobo; Min, Hui; Fu, Li; Yang, Zifeng

doi:10.1016/j.phymed.2020.153296

Cited by 86 publications

(61 citation statements)

References 34 publications

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“…It's investigated that KD-1 could attenuate the inflammatory reaction and pathological changes caused by influenza A virus and LPS-infected mice ( Qu et al, 2016 ; Zhong et al, 2013 ). Furthermore, KD-1 could protect against SARS-CoV-2 and human coronavirus 229E attack via suppressing the activity of NF-кB signaling pathway ( Ma et al, 2020 ). A recent study revealed that CGA and KD-1 has an effective ability to prevent the combination of SARS-CoV-2-spike protein and ACE2 through the molecular docking method ( Yu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

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

Gong²,

Qin

et al. 2021

Journal of Ethnopharmacology

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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...

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Section: Discussionmentioning

confidence: 99%

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

Gong²,

Qin

et al. 2021

Journal of Ethnopharmacology

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“…Recently, the SARS-CoV-2 virus was shown to use the NF-κβ pathway for the release of the pro-inflammatory cytokines such as TNFα and IL-6 ( Fig. 2 ) [ 64 ]. A previous study on SARS-CoV reported that S protein significantly increases NF-κβ activity and that the NF-κβ inhibition, leads to a strong inhibition of TNFα and IL-6 release [ 65 ].…”

Section: How Does Sars-cov-2 Initiate Cytokine Release and What Are Tmentioning

confidence: 99%

The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong?

Darif

Hammi

Kihel

et al. 2021

Microbial Pathogenesis

236

195

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The outbreak of coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, has emerged in China in December 2019 and rapidly spread to more than 196 countries worldwide. The physiopathology of human SARS-CoV-2 has not been completely understood, but its pathogenesis has been linked to a disproportionate response of the immune system. Just as described for SARS and MERS, an uncontrolled systemic inflammatory response, known as cytokine release syndrome (CRS) was observed in severe COVID-19 patients. It results from the release by immune and non-immune effector cells of substantial amounts of pro-inflammatory cytokines and appears to contribute to SARS-CoV-2 pulmonary inflammation and extensive lung damage. In addition, hyper-coagulation and thrombosis resulted from the important release of pro-inflammatory cytokines contribute to the lethality of subjects severely infected with SARS-CoV-2. It is therefore essential to have a deep understanding of the various cytokines involved in this exacerbated immune response, and that could be targeted by potential immunological treatments. The aim of this review was to gather the current knowledge about the role of pro-inflammatory cytokines, namely IL-1β, IL-6, IL-8, IL-17 and TNFα in SARS-CoV-2 CRS , the probable causes and clinical outcomes of this phenomenon in severe cases of COVID-19.

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“…Likewise, phillyrin (KD-1), a representative constituent of Forsythia suspensa (Thunb. ), presented an EC50 at 63.90 μ g/mL and CC50 of 1959 μ g/mL [ 38 ]. Sulfated polysaccharides named RPI-27 and heparin inhibited SARS-CoV-2 in vitro with an EC50 of 8.3 ± 4.6 μ g/mL and 36 ± 14 μ g/mL, respectively [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

The Hydroalcoholic Extract of Uncaria tomentosa (Cat’s Claw) Inhibits the Infection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) In Vitro

Yepes-Pérez

Herrera-Calderón

Oliveros

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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The coronavirus disease 2019 (COVID-19) has become a serious problem for public health since it was identified in the province of Wuhan (China) and spread around the world producing high mortality rates and economic losses. Nowadays, the WHO recognizes traditional, complementary, and alternative medicine for treating COVID-19 symptoms. Therefore, we investigated the antiviral potential of the hydroalcoholic extract of Uncaria tomentosa stem bark from Peru against SARS-CoV-2 in vitro. The antiviral activity of U. tomentosa against SARS-CoV-2 in vitro was assessed in Vero E6 cells using cytopathic effect (CPE) and plaque reduction assay. After 48 h of treatment, U. tomentosa showed an inhibition of 92.7% of SARS-CoV-2 at 25.0 μg/mL ( p < 0.0001 ) by plaque reduction assay on Vero E6 cells. In addition, U. tomentosa induced a reduction of 98.6% ( p = 0.02 ) and 92.7% ( p = 0.03 ) in the CPE caused by SARS-CoV-2 on Vero E6 cells at 25 μg/mL and 12.5 μg/mL, respectively. The EC50 calculated for the U. tomentosa extract by plaque reduction assay was 6.6 μg/mL (4.89–8.85 μg/mL) for a selectivity index of 4.1. The EC50 calculated for the U. tomentosa extract by TCID50 assay was 2.57 μg/mL (1.05–3.75 μg/mL) for a selectivity index of 10.54. These results showed that U. tomentosa, known as cat's claw, has an antiviral effect against SARS-CoV-2, which was observed as a reduction in the viral titer and CPE after 48 h of treatment on Vero E6 cells. Therefore, we hypothesized that U. tomentosa stem bark could be promising in the development of new therapeutic strategies against SARS-CoV-2.

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Phillyrin (KD-1) exerts anti-viral and anti-inflammatory activities against novel coronavirus (SARS-CoV-2) and human coronavirus 229E (HCoV-229E) by suppressing the nuclear factor kappa B (NF-κB) signaling pathway

Cited by 86 publications

References 34 publications

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

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

The pro-inflammatory cytokines in COVID-19 pathogenesis: What goes wrong?

The Hydroalcoholic Extract of Uncaria tomentosa (Cat’s Claw) Inhibits the Infection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) In Vitro

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