小柯机器人

新冠病毒蛋白相互作用图谱揭示药物再利用的靶点
2020-05-02 13:19
来源：小柯机器人

美国加州大学旧金山分校Nevan J. Krogan、Brian K. Shoichet、Kevan M. Shokat、西奈山伊坎医学院Adolfo García-Sastre、法国巴斯德研究所Marco Vignuzzi等研究人员，合作绘制了SARS-CoV-2蛋白质相互作用图谱，从而揭示了药物再利用的靶点。该研究于2020年4月30日在线发表于《自然》。

研究人员表示，新冠病毒SARS-CoV-2是COVID-19呼吸系统疾病的病原体，在全世界范围内造成了社会和经济破坏。目前，尚无具有经临床验证的抗病毒药物，也没有用于预防的疫苗，而且对SARS-CoV-2感染的分子细节了解有限。
 
为了解决这个问题，研究人员在人类细胞中克隆、标记和表达了29种SARS-CoV-2蛋白中的26种，并使用亲和纯化质谱（AP-MS）鉴定了与每种蛋白物理相关的人类蛋白，从而确定了332种高可信度SARS -CoV-2-人蛋白-蛋白相互作用（PPI）。
 
其中，研究人员确定了69种化合物（29种FDA批准的药物、12种临床试验的药物以及28种临床前化合物）靶向的66种可成药的人类蛋白质或宿主因子。在多个病毒测定中筛选这些子集，研究人员确定了两类具有抗病毒活性的药理制剂：mRNA翻译抑制剂和Sigma1和Sigma2受体的预测调节因子。
 
对这些宿主因子靶向剂的进一步研究，包括与直接靶向病毒酶的药物联合使用，可能会产生COVID-19的治疗方案。
 
附：英文原文

Title: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

Author: David E. Gordon, Gwendolyn M. Jang, Mehdi Bouhaddou, Jiewei Xu, Kirsten Obernier, Kris M. White, Matthew J. OMeara, Veronica V. Rezelj, Jeffrey Z. Guo, Danielle L. Swaney, Tia A. Tummino, Ruth Huettenhain, Robyn M. Kaake, Alicia L. Richards, Beril Tutuncuoglu, Helene Foussard, Jyoti Batra, Kelsey Haas, Maya Modak, Minkyu Kim, Paige Haas, Benjamin J. Polacco, Hannes Braberg, Jacqueline M. Fabius, Manon Eckhardt, Margaret Soucheray, Melanie J. Bennett, Merve Cakir, Michael J. McGregor, Qiongyu Li, Bjoern Meyer, Ferdinand Roesch, Thomas Vallet, Alice Mac Kain, Lisa Miorin

Issue&Volume: 2020-04-30

Abstract: The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.

DOI: 10.1038/s41586-020-2286-9

Source: https://www.nature.com/articles/s41586-020-2286-9

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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

分享到:

0