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Mapping and disrupting the SARS-CoV-2 protein interactome. [Funder: Institutional Funding]

Grant number: unknown

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Key facts

  • Disease

    COVID-19

  • Funder

    Other Funders (Canada)

  • Principal Investigator

    Brian Raught, Fritz Roth, Anne-Claude Gingras

  • Research Location

    Canada

  • Lead Research Institution

    University Health Network, Mount Sinai Hospital, University of Toronto

  • Research Priority Alignment

    N/A

  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen morphology, shedding & natural history

  • Special Interest Tags

    N/A

  • Study Type

    Non-Clinical

  • Clinical Trial Details

    Not applicable

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

While generic treatments for RNA virus infections are under investigation, no specific, effective treatment for SARS-CoV-2 is currently available. A lack of knowledge regarding how each of the ~26 SARS-CoV-2 virus proteins interact with the human host cell protein machinery significantly hampers our ability to rationally identify promising drug targets, and understand SARS-CoV-2 pathobiology at the molecular level. Using two complementary approaches - proximity-dependent biotinylation (BioID) and yeast two hybrid (Y2H) screening - here we propose to: (1) Conduct a global, systematic identification of SARS-CoV-2 virus-host protein-protein interactions (PPIs). (2) Combining the BioID and Y2H datasets, we will prioritize 100 validated PPIs that will be screened for disruption by FDA-approved drugs. (3) Drugs that disrupt virus-host PPIs will be tested for their ability to block SARS-CoV-2 infection in human airway epithelial cells in culture.