Potential Mechanism Prediction of Herbal Medicine for Pulmonary Fibrosis Associated with SARS-CoV-2 Infection Based on Network Analysis and Molecular Docking.
Potential Mechanism Prediction of Herbal Medicine for Pulmonary Fibrosis Associated with SARS-CoV-2 Infection Based on Network Analysis and Molecular Docking.
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DOI：
10.3389/fphar.2021.602218
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发表时间：
2021
影响因子：
5.6
通讯作者：
Tong X
中科院分区：
文献类型：
--
作者：
Jin D;An X;Zhang Y;Zhao S;Duan L;Duan Y;Lian F;Tong X
背景：2019 年冠状病毒病 (COVID-19) 仍然是一个相关的全球问题。尽管一些患者已经从 COVID-19 中康复，但 SARS-CoV-2 感染的后遗症可能包括肺纤维化，这可能会带来相当大的经济负担和医疗保健挑战。恢复期中药方（CCP）已在COVID-19恢复期广泛用于肺纤维化高危患者，并被《COVID-19诊疗方案》（试行第六版、第七版）推荐。然而，其根本机制仍不清楚。 方法：本研究采用综合药理学方法，通过评估CCP的吸收、分布、代谢和排泄，疾病靶点的数据挖掘，蛋白质-蛋白质相互作用（PPI）网络构建以及分析、富集分析和分子对接模拟，预测CCP治疗肺纤维化相关的生物活性成分、潜在靶点和分子机制。 患有 SARS-CoV-2 感染。 结果：通过数据库挖掘，获得了CCP的活性化合物和候选靶点，包括肺纤维化靶点。构建了药物-疾病网络。通过拓扑分析确定了 65 个关键目标。基因本体论(GO)术语和京都基因与基因组百科全书(KEGG)通路注释的发现提示VEGF、Toll样4受体、MAPK信号通路、TGF-β1信号通路可能参与肺纤维化。在分子对接分析中，VEGF、TNF-α、IL-6、MMP9表现出良好的结合活性。我们的研究结果表明，CCP 可通过 VEGF、Toll 样 4 受体、MAPK 和 TGF-β1 信号通路抑制 VEGF、TNF-α、IL-6、MMP9、TGF-β1 的表达。 结论：CCP 治疗 SARS-CoV-2 感染相关的 COVID-19 肺纤维化的潜在机制涉及多个成分、多个靶点以及多个途径。这些发现可能为进一步研究 CCP 的抗纤维化机制提供概况。
Background: Coronavirus Disease 2019 (COVID-19) is still a relevant global problem. Although some patients have recovered from COVID-19, the sequalae to the SARS-CoV-2 infection may include pulmonary fibrosis, which may contribute to considerable economic burden and health-care challenges. Convalescent Chinese Prescription (CCP) has been widely used during the COVID-19 recovery period for patients who were at high risk of pulmonary fibrosis and is recommended by the Diagnosis and Treatment Protocol for COVID-19 (Trial Version sixth, seventh). However, its underlying mechanism is still unclear. Methods: In this study, an integrated pharmacology approach was implemented, which involved evaluation of absorption, distribution, metabolism and excretion of CCP, data mining of the disease targets, protein-protein interaction (PPI) network construction, and analysis, enrichment analysis, and molecular docking simulation, to predict the bioactive components, potential targets, and molecular mechanism of CCP for pulmonary fibrosis associated with SARS-CoV-2 infection. Results: The active compound of CCP and the candidate targets, including pulmonary fibrosis targets, were obtained through database mining. The Drug-Disease network was constructed. Sixty-five key targets were identified by topological analysis. The findings of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation suggested that the VEGF, Toll-like 4 receptor, MAPK signaling pathway, and TGF-β1 signaling pathways may be involved in pulmonary fibrosis. In the molecular docking analyses, VEGF, TNF-α, IL-6, MMP9 exhibited good binding activity. Findings from our study indicated that CCP could inhibit the expression of VEGF, TNF-α, IL-6, MMP9, TGF-β1 via the VEGF, Toll-like 4 receptor, MAPK, and TGF-β1 signaling pathways. Conclusion: Potential mechanisms involved in CCP treatment for COVID-19 pulmonary fibrosis associated with SARS-CoV-2 infection involves multiple components and multiple target points as well as multiple pathways. These findings may offer a profile for further investigations of the anti-fibrotic mechanism of CCP.
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DOI：
10.4049/jimmunol.1302470
发表时间：
2014-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Le TT;Karmouty-Quintana H;Melicoff E;Le TT;Weng T;Chen NY;Pedroza M;Zhou Y;Davies J;Philip K;Molina J;Luo F;George AT;Garcia-Morales LJ;Bunge RR;Bruckner BA;Loebe M;Seethamraju H;Agarwal SK;Blackburn MR
通讯作者：
Blackburn MR
影响因子：
10.8
作者：
Bates DO
通讯作者：
Bates DO
影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
DOI：
10.1183/09031936.00196412
发表时间：
2014-01
期刊：
The European respiratory journal
影响因子：
--
作者：
Burnham EL;Janssen WJ;Riches DW;Moss M;Downey GP
通讯作者：
Downey GP
影响因子：
9.6
作者：
Canestaro, William J.;Forrester, Sara H.;Devine, Beth E.
通讯作者：
Devine, Beth E.