A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.
A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.
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DOI：
10.1101/2020.03.22.002386
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发表时间：
2020-03-27
期刊：
影响因子：
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通讯作者：
Krogan, Nevan J
中科院分区：
文献类型：
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作者：
Gordon, David E;Jang, Gwendolyn M;Krogan, Nevan J
新型冠状病毒SARS-CoV-2是新冠肺炎呼吸道疾病的病原体，自2019年底爆发以来，已有超过29万人感染，超过1.2万人死亡，并造成全球社会和经济混乱1，2。目前还没有有效的抗病毒药物，也没有预防它的疫苗。不幸的是，科学界对SARS-CoV-2感染的分子细节知之甚少。为了阐明这一点，我们克隆、标记并在人类细胞中表达了29种病毒蛋白中的26种，并使用亲和纯化质谱仪(AP-MS)鉴定了与每种蛋白物理相关的人类蛋白，鉴定了332种高置信度的SARS-CoV-2-人蛋白-蛋白相互作用(PPI)。其中，我们确定了69种现有FDA批准的药物、临床试验中的药物和/或临床前化合物所针对的67种可药物人类蛋白或宿主因子，我们目前正在评估这些药物在SARS-CoV-2活体感染检测中的有效性。识别介导病毒感染的宿主依赖因子可能为开发针对SARS-CoV-2和其他致命冠状病毒株的广谱抗病毒药物提供有效的分子靶点。
An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.