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通过综合生物信息学分析筛选 COVID-19 的可用药靶标和预测治疗药物。

Screening druggable targets and predicting therapeutic drugs for COVID-19 via integrated bioinformatics analysis.

机构信息

Department of Anesthesiology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, No.61 Jiefang West Road, Furong District, Changsha, 410002, Hunan, China.

Department of Cardiothoracic Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410002, Hunan, China.

出版信息

Genes Genomics. 2021 Jan;43(1):55-67. doi: 10.1007/s13258-020-01021-8. Epub 2021 Jan 11.

DOI:10.1007/s13258-020-01021-8
PMID:33428154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7797890/
Abstract

BACKGROUND

Since the outbreak of coronavirus disease 2019 (COVID-19) in China, numerous research institutions have invested in the development of anti-COVID-19 vaccines and screening for efficacious drugs to manage the virus.

OBJECTIVE

To explore the potential targets and therapeutic drugs for the prevention and treatment of COVID-19 through data mining and bioinformatics.

METHODS

We integrated and profoundly analyzed 10 drugs previously assessed to have promising therapeutic potential in COVID-19 management, and have been recommended for clinical trials. To explore the mechanisms by which these drugs may be involved in the treatment of COVID-19, gene-drug interactions were identified using the DGIdb database after which functional enrichment analysis, protein-protein interaction (PPI) network, and miRNA-gene network construction were performed. We adopted the DGIdb database to explore the candidate drugs for COVID-19.

RESULTS

A total of 43 genes associated with the 10 potential COVID-19 drugs were identified. Function enrichment analysis revealed that these genes were mainly enriched in response to other invasions, toll-like receptor pathways, and they play positive roles in the production of cytokines such as IL-6, IL-8, and INF-β. TNF, TLR3, TLR7, TLR9, and CXCL10 were identified as crucial genes in COVID-19. Through the DGIdb database, we predicted 87 molecules as promising druggable molecules for managing COVID-19.

CONCLUSIONS

Findings from this work may provide new insights into COVID-19 mechanisms and treatments. Further, the already identified candidate drugs may improve the efficiency of pharmaceutical treatment in this rapidly evolving global situation.

摘要

背景

自 2019 年冠状病毒病(COVID-19)在中国爆发以来,众多研究机构投入到抗 COVID-19 疫苗的开发和有效药物的筛选中,以应对该病毒。

目的

通过数据挖掘和生物信息学方法,探索预防和治疗 COVID-19 的潜在靶点和治疗药物。

方法

我们整合并深入分析了此前评估有治疗 COVID-19 管理潜力并已推荐用于临床试验的 10 种药物。为了探索这些药物可能参与治疗 COVID-19 的机制,我们使用 DGIdb 数据库识别了基因-药物相互作用,然后进行了功能富集分析、蛋白质-蛋白质相互作用(PPI)网络和 miRNA-基因网络构建。我们采用 DGIdb 数据库来探索 COVID-19 的候选药物。

结果

共鉴定出与 10 种潜在 COVID-19 药物相关的 43 个基因。功能富集分析表明,这些基因主要富集在对其他入侵的反应、 toll 样受体途径中,并且它们在细胞因子如 IL-6、IL-8 和 INF-β的产生中发挥积极作用。TNF、TLR3、TLR7、TLR9 和 CXCL10 被鉴定为 COVID-19 的关键基因。通过 DGIdb 数据库,我们预测了 87 种分子作为管理 COVID-19 的有前途的可成药分子。

结论

本研究的结果可能为 COVID-19 的机制和治疗提供新的见解。此外,已经确定的候选药物可能会提高在这种快速演变的全球形势下药物治疗的效率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/7e4a2e8f9e60/13258_2020_1021_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/0a5fe6a3582b/13258_2020_1021_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/dae0fec8a0e1/13258_2020_1021_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/386e5e6d8433/13258_2020_1021_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/7e4a2e8f9e60/13258_2020_1021_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/0a5fe6a3582b/13258_2020_1021_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/5248c81c7ef4/13258_2020_1021_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/64b05878a498/13258_2020_1021_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/d605863f1320/13258_2020_1021_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/dae0fec8a0e1/13258_2020_1021_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/386e5e6d8433/13258_2020_1021_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f142/7797890/7e4a2e8f9e60/13258_2020_1021_Fig7_HTML.jpg

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