小柯机器人

蛋白质组学揭示新冠病毒治疗靶点
2020-05-15 10:53

德国歌德大学Christian Münch、Jindrich Cinatl等研究人员合作利用新冠病毒(SARS-CoV-2)感染后细胞的蛋白质组学分析揭示出潜在治疗靶点。这一研究成果于2020年5月14日在线发表在《自然》上。

研究人员确定了由SARS-CoV-2感染影响的宿主细胞途径,并表明这些途径的抑制阻止了病毒在人类细胞中的复制。研究人员建立了感染SARS-CoV-2临床分离株的人类细胞培养模型。使用该系统,研究人员在感染后的不同时间通过翻译组和蛋白质组蛋白质组学确定了SARS-CoV-2感染情况。
 
这些分析表明,SARS-CoV-2重塑了关键细胞通路,例如翻译、剪接、碳代谢和核酸代谢。靶向这些途径的小分子抑制剂阻止了病毒在细胞中复制。这些结果揭示了SARS-CoV-2的细胞感染情况,从而鉴定出抑制病毒复制的药物。研究人员认为这些结果将促进人们理解SARS-CoV-2感染后宿主细胞改变的分子机制。此外,这些发现为开发COVID-19的治疗方案提供了见解。
 
附:英文原文

Title: Proteomics of SARS-CoV-2-infected host cells reveals therapy targets

Author: Denisa Bojkova, Kevin Klann, Benjamin Koch, Marek Widera, David Krause, Sandra Ciesek, Jindrich Cinatl, Christian Mnch

Issue&Volume: 2020-05-14

Abstract: A novel coronavirus was recently discovered and termed SARS-CoV-2. Human infection can cause coronavirus disease 2019 (COVID-19), which has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses. However, treatment options and a cellular understanding of SARS-CoV-2 infection are lacking. Here we identify the host cell pathways modulated by SARS-CoV-2 infection and show that inhibition of these pathways prevent viral replication in human cells. We established a human cell culture model for infection with SARS-CoV-2 clinical isolate. Employing this system, we determined the SARS-CoV-2 infection profile by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways, such as translation, splicing, carbon metabolism and nucleic acid metabolism. Small molecule inhibitors targeting these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and led to the identification of drugs inhibiting viral replication. We anticipate our results to guide efforts to understand the molecular mechanisms underlying host cell modulation upon SARS-CoV-2 infection. Furthermore, our findings provide insight for the development of therapy options for COVID-19.

DOI: 10.1038/s41586-020-2332-7

Source:https://www.nature.com/articles/s41586-020-2332-7

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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