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

Project Summary: The Reactome Knowledgebase is a widely used and internationally recognized expert-curated, open-sourceresource of a broad array of human biological processes and their disease counterparts, coupled to powerful toolsfor data analysis and display, and integrated with diverse community genomics resources. The work proposedhere will add molecular annotations of the COVID-19 infection process mediated by the SARS-CoV-2coronavirus, interactions between viral components and human host proteins that mediate the severity of viralinfection, and the effects of therapeutics and drug-like compounds on both viral and host proteins. The resultingSARS-CoV-2 pathway annotations will provide a framework for pathway- and network-based data analysis andvisualization, 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 willassemble 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. Theseannotations will be immediately useful for identifying additional relevant interacting proteins, for assessingpossible effects of variation in the host or viral proteins on specific steps of viral infection, and for identifyingpossible drug targets. In the second stage, the SARS-CoV-2 map will be annotated more extensively to fill inmolecular 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 toincorporate 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.