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

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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.