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从病毒转录组推断严重急性呼吸综合征冠状病毒2(SARS-CoV-2)功能基因组学并鉴定潜在抗病毒药物和治疗靶点。

Inferring SARS-CoV-2 functional genomics from viral transcriptome with identification of potential antiviral drugs and therapeutic targets.

作者信息

Pan Xu, Li Xin, Ning Shangwei, Zhi Hui

机构信息

College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

Department of Dermatology, Xiangya Hospital, Central South University, Changsha, 410008, China.

出版信息

Cell Biosci. 2021 Sep 8;11(1):171. doi: 10.1186/s13578-021-00684-4.

Abstract

Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and has posed a serious threat to global health. Here, we systematically characterized the transcription levels of the SARS-CoV-2 genes and identified the responsive human genes associated with virus infection. We inferred the possible biological functions of each viral gene and depicted the functional landscape based on guilt-by-association and functional enrichment analyses. Subsequently, the transcription factor regulatory network, protein-protein interaction network, and non-coding RNA regulatory network were constructed to discover more potential antiviral targets. In addition, several potential drugs for COVID-19 treatment and prevention were recognized, including known cell proliferation-related, immune-related, and antiviral drugs, in which proteasome inhibitors (bortezomib, carfilzomib, and ixazomib citrate) may play an important role in the treatment of COVID-19. These results provided novel insights into the understanding of SARS-CoV-2 functional genomics and host-targeting antiviral strategies for SARS-CoV-2 infection.

摘要

2019冠状病毒病(COVID-19)是由严重急性呼吸综合征冠状病毒2(SARS-CoV-2)引起的一种新发传染病,对全球健康构成了严重威胁。在此,我们系统地表征了SARS-CoV-2基因的转录水平,并鉴定了与病毒感染相关的反应性人类基因。我们推断了每个病毒基因的可能生物学功能,并基于关联有罪和功能富集分析描绘了功能景观。随后,构建了转录因子调控网络、蛋白质-蛋白质相互作用网络和非编码RNA调控网络,以发现更多潜在的抗病毒靶点。此外,还识别出了几种用于COVID-19治疗和预防的潜在药物,包括已知的细胞增殖相关、免疫相关和抗病毒药物,其中蛋白酶体抑制剂(硼替佐米、卡非佐米和枸橼酸伊沙佐米)可能在COVID-19治疗中发挥重要作用。这些结果为理解SARS-CoV-2功能基因组学以及针对SARS-CoV-2感染的宿主靶向抗病毒策略提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ba8/8425066/7a4f073154c2/13578_2021_684_Fig1_HTML.jpg

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