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Genome-scale identification of SARS-CoV-2 and pan-coronavirus host factor networks

The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a member of the Coronaviridae family of viruses that can cause respiratory infections of varying severity...

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Main Authors: Schneider, William M. (Author) , Luna, Joseph M. (Author) , Hoffmann, H. -Heinrich (Author) , Sánchez-Rivera, Francisco J. (Author) , Leal, Andrew A. (Author) , Ashbrook, Alison W. (Author) , Le Pen, Jérémie (Author) , Ricardo-Lax, Inna (Author) , Michailidis, Eleftherios (Author) , Peace, Avery (Author) , Stenzel, Ansgar (Author) , Lowe, Scott W. (Author) , MacDonald, Margaret R. (Author) , Rice, Charles M. (Author) , Poirier, John T. (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Cell
Year: 2021, Volume: 184, Issue: 1, Pages: 120-132.e14
ISSN:1097-4172
DOI:10.1016/j.cell.2020.12.006
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cell.2020.12.006
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0092867420316767
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Author Notes:William M. Schneider, Joseph M. Luna, H. -Heinrich Hoffmann, Francisco J. Sánchez-Rivera, Andrew A. Leal, Alison W. Ashbrook, Jérémie Le Pen, Inna Ricardo-Lax, Eleftherios Michailidis, Avery Peace, Ansgar F. Stenzel, Scott W. Lowe, Margaret R. MacDonald, Charles M. Rice, and John T. Poirier

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520 |a The coronavirus disease 2019 (COVID-19) pandemic has claimed the lives of over one million people worldwide. The causative agent, severe acute respiratory syndrome coronavirus 2 (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, sterol regulatory element-binding protein (SREBP) signaling, bone morphogenetic protein (BMP) signaling, and glycosylphosphatidylinositol biosynthesis, as well as a requirement for several poorly characterized proteins. We identified an absolute requirement for the VMP1, TMEM41, and TMEM64 (VTT) domain-containing protein transmembrane protein 41B (TMEM41B) for infection by SARS-CoV-2 and three seasonal coronaviruses. This human coronavirus host factor compendium represents a rich resource to develop new therapeutic strategies for acute COVID-19 and potential future coronavirus pandemics. 
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