Genetic screens to find critical host factors for SARS-CoV-2 infection

  • Funded by National Institutes of Health (NIH)
  • Total publications:0 publications

Grant number: unknown

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2023
  • Known Financial Commitments (USD)

    $121,561
  • Funder

    National Institutes of Health (NIH)
  • Principle Investigator

    Pending
  • Research Location

    United States of America, Americas
  • Lead Research Institution

    STANFORD UNIVERSITY
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen morphology, shedding & natural history

  • Special Interest Tags

    Gender

  • Study Subject

    Non-Clinical

  • Clinical Trial Details

    N/A

  • Broad Policy Alignment

    Pending

  • Age Group

    Not Applicable

  • Vulnerable Population

    Not applicable

  • Occupations of Interest

    Not applicable

Abstract

PROJECT SUMMARY Emerging and re-emerging viruses cause a constant threat to global health. Discovery and characterization ofcellular signaling pathways that regulate pathogenesis and host defense hold promise for revealing new strategies aimed at enhancing resistance to infection. There are no approved antiviral therapies available forcoronaviruses, including SARS-CoV-2, that cause disease on a large scale, highlighting the need for innovative approaches to develop more broad-spectrum antivirals. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication. Recent breakthroughs in somatic cell genetics have enabled genome-scale genetic knockout screens in human cells to identify cellular factors critical to infection and to dissect innate immune pathways. The pooled genetic knockout approach has several key advantages. First, by using a genome-scale CRISPR library and using pseudotyped virus for entry and a SARS-CoV-2 replicon for RNA replication and transcription, only those genes are selected whose knockout confers a strong resistance to virus infection.Second, because this approach relies on complete knockout of the gene of interest, we select only those genes that affect infection without being required for cellular viability and growth. In this competitive supplement, we propose to use these robust and unbiased knockout screening approaches to identify and thoroughly characterize novel host targets essential for infection by SARS-CoV-2. We expect that these genome-scale screens will elucidate promising cellular targets that could be used to develop host-directed antiviral therapy.