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《Cell，10月20日，Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection》

  • 来源专题：COVID-19科研动态监测
  • 编译者： zhangmin
  • 发布时间：2020-11-16

  • Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection
    Jin Wei
    Mia Madel Alfajaro
    Peter C. DeWeirdt
    Qin Yan
    John G. Doench
    Craig B. Wilen 18
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    Published:October 20, 2020DOI:https://doi.org/10.1016/j.cell.2020.10.028

    Summary
    Identification of host genes essential for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may reveal novel therapeutic targets and inform our understanding of coronavirus disease 2019 (COVID-19) pathogenesis. Here we performed genome-wide CRISPR screens in Vero-E6 cells with SARS-CoV-2, Middle East respiratory syndrome CoV (MERS-CoV), bat CoV HKU5 expressing the SARS-CoV-1 spike, and vesicular stomatitis virus (VSV) expressing the SARS-CoV-2 spike. We identified known SARS-CoV-2 host factors, including the receptor ACE2 and protease Cathepsin L. We additionally discovered pro-viral genes and pathways, including HMGB1 and the SWI/SNF chromatin remodeling complex, that are SARS lineage and pan-coronavirus specific, respectively. We show that HMGB1 regulates ACE2 expression and is critical for entry of SARS-CoV-2, SARS-CoV-1, and NL63. We also show that small-molecule antagonists of identified gene products inhibited SARS-CoV-2 infection in monkey and human cells, demonstrating the conserved role of these genetic hits across species. This identifies potential therapeutic targets for SARS-CoV-2 and reveals SARS lineage-specific and pan-CoV host factors that regulate susceptibility to highly pathogenic CoVs.

  • 原文来源：https://www.cell.com/cell/fulltext/S0092-8674(20)31392-1
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