Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks
William M. Schneider 5
Joseph M. Luna 5
H.-Heinrich Hoffmann 5
Margaret R. MacDonald
Charles M. Rice
John T. Poirier 7
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Published:December 09, 2020DOI:https://doi.org/10.1016/j.cell.2020.12.006
Summary
The COVID-19 pandemic has claimed the lives of over one million people worldwide. The causative agent, SARS-CoV-2, is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity. The cellular host factors and pathways co-opted during SARS-CoV-2 and related coronavirus life cycles remain ill-defined. To address this gap, we performed genome-scale CRISPR knockout screens during infection by SARS-CoV-2 and three seasonal coronaviruses (HCoV-OC43, HCoV-NL63, and HCoV-229E). These screens uncovered host factors and pathways with pan-coronavirus and virus-specific functional roles, including major dependency on glycosaminoglycan biosynthesis, SREBP signaling, BMP signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VTT-domain containing protein TMEM41B for infection by SARS-CoV-2 and three seasonal coronaviruses. This human Coronaviridae host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics.