Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection.
Cell
; 184(1): 76-91.e13, 2021 01 07.
Article
in En
| MEDLINE
| ID: mdl-33147444
ABSTRACT
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.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Coronavirus Infections
/
Host-Pathogen Interactions
/
Genome-Wide Association Study
/
SARS-CoV-2
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Year:
2021
Type:
Article