Integrated multi-omic delineation of SARS-CoV-2-dysregulated cellular processes

Coombs, Kevin M | $790,162

Manitoba University of Manitoba 2020 CIHR Operating Grant

As of May 10 2020, there were a reported >4 million confirmed cases and > 285,000 deaths attributed to the novel coronavirus (CoV) SARS-CoV-2, causing the COVID‑19 disease. Our understanding of the molecular factors that are responsible for the virulence and the selection of host cells to be infected by SARS-CoV-2 that could explain the emerging variety of clinical symptoms reported in COVID‑19 patients is rudimentary at best. All strategies of rapidly developing tools to mitigate this catastrophic SARS-CoV-2 pandemic are fundamentally dependent on us identifying and controlling those proteins that execute the cellular mechanisms critical for SARS-CoV-2 virus to infect and replicate in host cells. We will use a powerful novel tool, called SOMAscan, to rapidly determine how COVID‑19 (SARS-CoV-2 coronavirus), and a variety of other coronaviruses, affect large numbers of proteins in different human lung cells, the normal target of the COVID‑19 virus. By examining how non-pathogenic, and highly pathogenic, coronaviruses, such as SARS-1, MERS and SARS-CoV-2 specifically and differentially affect cellular proteins, we will learn the unique ways in which the deadly coronaviruses can cause disease. We also will examine how these cellular proteins, and virus infection, are influenced by treatment with a variety of anti-viral agents, some of which are currently in clinical trials, to improve the information gained in these complementary clinical trials. Finally, we also will determine how affecting some of the proteins we identify can impact coronavirus-mediated growth and disease processes. Results obtained in this research will provide vital fundamental information about the molecular replication of the SARS-CoV-2 virus and will form the foundation for more in-depth studies, all of which will pave the way for more effective therapeutic interventions to improve human health.

With funding from the Government of Canada

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