Function interactions between mitogen-activated protein kinases (MAPKs) and SARS-CoV-2

项目总结 新冠肺炎大流行的病原体SARS-CoV-2以深刻的方式改变了它感染的细胞。 一种这样的修饰是激活宿主细胞丝裂原活化蛋白激酶(MAPK)途径，这是 导致严重的炎症，这是严重新冠肺炎病的一个特征。一种MAPK的抑制作用 P38/MAPK途径通过一种未知的机制减少SARS-CoV-2的复制。这项建议 旨在利用多学科研究来衡量人类MAPK通路对SARS-CoV-2感染的影响 该方法结合了最先进的蛋白质组学技术、中通量基因筛查和 SARS-CoV-2感染的体内和体外模型。这些发现将为MAPK的潜在应用提供信息 新冠肺炎治疗的抑制剂，并可能在MAPK家族中寻找替代靶点。MAPK通路 在许多疾病状态中发挥关键作用，这项工作将通过提供分子信息来指导这些领域的研究 MAPK调节机制和为无偏见地发现MAPK底物和提供工具 监管者。

PROJECT SUMMARY SARS-CoV-2, the causative agent of the COVID-19 pandemic, modifies the cells that it infects in profound ways. One such modification is the activation of host cellular mitogen-activated protein kinase (MAPK) pathways, which contribute to severe inflammation that is a hallmark of severe COVID-19 disease. Inhibition of one MAPK pathway, the p38/MAPK pathway, reduces SARS-CoV-2 replication by an undefined mechanism. This proposal aims to measure the impact of human MAPK pathways on SARS-CoV-2 infection using a multidisciplinary approach that combines state-of-the-art proteomics technologies, medium-throughput genetic screening, and in vivo and ex vivo models of SARS-CoV-2 infection. These findings will inform the potential application of MAPK inhibitors for COVID-19 treatment and may identify alternative targets within the MAPK families. MAPK pathways play critical roles in many disease states, and this work will inform research in these areas by providing molecular mechanisms for MAPK regulation and providing tools for the unbiased discovery of MAPK substrates and regulators.