Rapid and Precise Molecular Pathway Modelling of the SARS-CoV-1 and SARS-CoV-2 Infection Cycle with Human Host Protein and Therapeutic Interactions

项目摘要 Reactome知识库是一个广泛使用和国际公认的专家策划的、开源的 广泛的人类生物过程及其对应疾病的资源，再加上强大的工具 用于数据分析和展示，并与不同的社区基因组资源集成。建议的工作 这里将添加由SARS-CoV-2介导的新冠肺炎感染过程的分子注释 冠状病毒，病毒成分与人类宿主蛋白之间的相互作用，调节病毒的严重程度 感染，以及治疗药物和类药物化合物对病毒和宿主蛋白的影响。由此产生的 SARS-CoV-2途径注释将为基于途径和网络的数据分析和 可视化，这对于解释现在和未来的许多新冠肺炎研究都将是至关重要的。 通过与病毒学、药物设计和传染病方面的社区专家团队合作，我们将 分两个阶段收集信息。首先，草案注释将相关的SARS-CoV-1和SARS-CoV- 2病毒和宿主细胞蛋白与感染过程的每个阶段和宿主对它的反应。这些 注释将立即用于识别其他相关的相互作用蛋白质，用于评估 宿主或病毒蛋白变异对病毒感染的特定步骤的可能影响，并用于识别 可能的毒品目标。在第二阶段，将对SARS-CoV-2地图进行更广泛的注记以填写 这些过程中每个步骤的分子细节，并强调SARS介导的过程中的差异- CoV-2病毒及相关冠状病毒。这一注解过程将在项目期间继续进行，以 纳入新验证的分子细节，因为它们是由研究界发现的。 该项目开发的所有数据、代码和工具都将是开源和开放的。

Project Summary The Reactome Knowledgebase is a widely used and internationally recognized expert-curated, open-source resource of a broad array of human biological processes and their disease counterparts, coupled to powerful tools for data analysis and display, and integrated with diverse community genomics resources. The work proposed here will add molecular annotations of the COVID-19 infection process mediated by the SARS-CoV-2 coronavirus, interactions between viral components and human host proteins that mediate the severity of viral infection, and the effects of therapeutics and drug-like compounds on both viral and host proteins. The resulting SARS-CoV-2 pathway annotations will provide a framework for pathway- and network-based data analysis and visualization, which will be critical for the interpretation of numerous COVID-19 studies now and in the future. In collaboration with a team of community experts in virology, drug design, and infectious disease, we will assemble information in two stages. First, a draft annotation will associate relevant SARS-CoV-1 and SARS-CoV- 2 viral and host cell proteins with each stage of the infection process and the host response to it. These annotations will be immediately useful for identifying additional relevant interacting proteins, for assessing possible effects of variation in the host or viral proteins on specific steps of viral infection, and for identifying possible drug targets. In the second stage, the SARS-CoV-2 map will be annotated more extensively to fill in molecular details of each step in these processes and to highlight differences in the processes mediated by SARS- CoV-2 virus and related coronaviruses. This annotation process will continue for the duration of the project to incorporate newly validated molecular details as they are uncovered by the research community. All the data, code and tools developed by this project will be open source and open.