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基于系统生物学的新冠肺炎相关通路及治疗药物的筛选分析

Integrated Bioinformatics Analysis for the Screening of Associated Pathways and Therapeutic Drugs in Coronavirus Disease 2019.

机构信息

Department of Life Science and Bio-Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.

Department of Medical Devices, Shenyang Pharmaceutical University, Benxi, Liaoning, China.

出版信息

Arch Med Res. 2021 Apr;52(3):304-310. doi: 10.1016/j.arcmed.2020.11.009. Epub 2020 Dec 4.

Abstract

BACKGROUND

COVID-19 caused by a novel coronavirus, a severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has recently broken out worldwide. Up to now, the development of vaccine is still in the stage of clinical research, and there is no clinically approved specific antiviral drug for human coronavirus infection. The purpose of this study is to investigate the key molecules involved in response during SARS-CoV-2 infection and provide references for the treatment of SARS-CoV-2.

METHODS

We conducted in-depth and comprehensive bioinformatics analysis of human proteins identified with SARS-CoV-2, including functional enrichment analysis, protein interaction network analysis, screening of hub genes, and evaluation of their potential as therapeutic targets. In addition, we used the gene-drug database to search for inhibitors of related biological targets.

RESULTS

Several significant pathways, such as PKA, centrosome and transcriptional regulation, may greatly contribute to the development and progression of COVID-2019 disease. Taken together 15 drugs and 18 herb ingredients were screened as potential drugs for viral treatment. Specially, the trans-resveratrol can significantly reduce the expression of N protein of MERS-CoV and inhibit MERS-CoV. In addition, trans-resveratrol, Epigallocatechin-3-gallate (EGCG) and BX795 all show good anti multiple virus effects.

CONCLUSION

Some drugs selected through our methods have been proven to have antiviral effects in previous studies. We aim to use global bioinformatics analysis to provide insights to assist in the design of new drugs and provide new choices for clinical treatment.

摘要

背景

由新型冠状病毒(SARS-CoV-2)引起的 COVID-19 已在全球范围内爆发。到目前为止,疫苗的开发仍处于临床研究阶段,对于人类冠状病毒感染,还没有经临床批准的特异性抗病毒药物。本研究旨在探讨 SARS-CoV-2 感染过程中涉及的关键分子,为 SARS-CoV-2 的治疗提供参考。

方法

我们对鉴定出的与人 SARS-CoV-2 相互作用的人类蛋白进行了深入全面的生物信息学分析,包括功能富集分析、蛋白互作网络分析、枢纽基因的筛选及其作为治疗靶点的潜力评估。此外,我们还使用基因-药物数据库来搜索相关生物靶点的抑制剂。

结果

一些重要的途径,如 PKA、中心体和转录调控,可能对 COVID-19 疾病的发展和进展有重大贡献。综合考虑,筛选出 15 种药物和 18 种草药成分作为病毒治疗的潜在药物。特别是反式白藜芦醇可显著降低 MERS-CoV 的 N 蛋白表达,并抑制 MERS-CoV。此外,反式白藜芦醇、表没食子儿茶素没食子酸酯(EGCG)和 BX795 均显示出良好的抗多种病毒作用。

结论

我们通过方法筛选出的一些药物在之前的研究中已被证明具有抗病毒作用。我们旨在通过全球生物信息学分析提供见解,以辅助新药设计,并为临床治疗提供新的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eeaf/7833343/20e472a99c6f/gr1_lrg.jpg

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