论文标题

探索SARS-COV-2病毒 - 宿主 - 宿主互动以进行药物重新利用

Exploring the SARS-CoV-2 virus-host-drug interactome for drug repurposing

论文作者

Sadegh, Sepideh, Matschinske, Julian, Blumenthal, David B., Galindez, Gihanna, Kacprowski, Tim, List, Markus, Nasirigerdeh, Reza, Oubounyt, Mhaned, Pichlmair, Andreas, Rose, Tim Daniel, Salgado-Albarrán, Marisol, Späth, Julian, Stukalov, Alexey, Wenke, Nina K., Yuan, Kevin, Pauling, Josch K., Baumbach, Jan

论文摘要

冠状病毒疾病2019年(Covid-19)是由SARS-COV-2病毒引起的一种传染病。它最初是在中国武汉确定的,此后散布引起全球大流行。已经进行了各种研究,以了解病毒感染的分子机制,以预测药物重新利用的候选者。但是,这些信息分布在许多出版物中,访问,集成,探索和利用非常耗时。我们开发了Covex,这是SARS-COV-2和SARS-COV-1主机Interactome Exploration and Drug(目标)识别的第一个交互式在线平台。 COVEX整合1)经过实验验证的病毒人类蛋白相互作用,2)人类蛋白质 - 蛋白质相互作用和3)药物靶标相互作用。 Web界面允许对病毒宿主相互作用的用户友好型视觉探索,并实现了基于网络的药物预测的系统医学算法。因此,Covex是一个重要的资源,不仅是为了了解SARS-COV-2和SARS-COV-1致病性涉及的分子机制,而且还了解了鉴定和优先鉴定候选疗法的临床研究。我们应用Covex来研究系统生物学水平上的最新假设,并系统地探索驱动病毒生命周期的分子机制。此外,我们提取和讨论参与这些机制的药物重新利用。 Covex通过使科学界直接访问网络医学算法来整合病毒宿主 - 宿主 - 药水相互作用,从而使COVID-19 Covid-19药物研究系统中准备好。它可在https://exbio.wzw.tum.de/covex/上找到。

Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by the SARS-CoV-2 virus. It was first identified in Wuhan, China, and has since spread causing a global pandemic. Various studies have been performed to understand the molecular mechanisms of viral infection for predicting drug repurposing candidates. However, such information is spread across many publications and it is very time-consuming to access, integrate, explore, and exploit. We developed CoVex, the first interactive online platform for SARS-CoV-2 and SARS-CoV-1 host interactome exploration and drug (target) identification. CoVex integrates 1) experimentally validated virus-human protein interactions, 2) human protein-protein interactions and 3) drug-target interactions. The web interface allows user-friendly visual exploration of the virus-host interactome and implements systems medicine algorithms for network-based prediction of drugs. Thus, CoVex is an important resource, not only to understand the molecular mechanisms involved in SARS-CoV-2 and SARS-CoV-1 pathogenicity, but also in clinical research for the identification and prioritization of candidate therapeutics. We apply CoVex to investigate recent hypotheses on a systems biology level and to systematically explore the molecular mechanisms driving the virus life cycle. Furthermore, we extract and discuss drug repurposing candidates involved in these mechanisms. CoVex renders COVID-19 drug research systems-medicine-ready by giving the scientific community direct access to network medicine algorithms integrating virus-host-drug interactions. It is available at https://exbio.wzw.tum.de/covex/.

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