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Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designe...

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Main Authors: Hoffmann, Hans-Heinrich (Author) , Sánchez-Rivera, Francisco J. (Author) , Schneider, William M. (Author) , Luna, Joseph M. (Author) , Soto-Feliciano, Yadira M. (Author) , Ashbrook, Alison W. (Author) , Le Pen, Jérémie (Author) , Leal, Andrew A. (Author) , Ricardo-Lax, Inna (Author) , Michailidis, Eleftherios (Author) , Hao, Yuan (Author) , Stenzel, Ansgar (Author) , Peace, Avery (Author) , Zuber, Johannes (Author) , Allis, C. David (Author) , Lowe, Scott W. (Author) , MacDonald, Margaret R. (Author) , Poirier, John T. (Author) , Rice, Charles M. (Author)
Format: Article (Journal)
Language:English
Published: 2021
In: Cell host and microbe
Year: 2021, Volume: 29, Issue: 2, Pages: 267-280.e5
ISSN:1934-6069
DOI:10.1016/j.chom.2020.12.009
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.chom.2020.12.009
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1931312820306715
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Author Notes:H.-Heinrich Hoffmann, Francisco J. Sánchez-Rivera, William M. Schneider, Joseph M. Luna, Yadira M. Soto-Feliciano, Alison W. Ashbrook, Jérémie Le Pen, Andrew A. Leal, Inna Ricardo-Lax, Eleftherios Michailidis, Yuan Hao, Ansgar F. Stenzel, Avery Peace, Johannes Zuber, C. David Allis, Scott W. Lowe, Margaret R. MacDonald, John T. Poirier, and Charles M. Rice

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520 |a The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has devastated the global economy and claimed more than 1.7 million lives, presenting an urgent global health crisis. To identify host factors required for infection by SARS-CoV-2 and seasonal coronaviruses, we designed a focused high-coverage CRISPR-Cas9 library targeting 332 members of a recently published SARS-CoV-2 protein interactome. We leveraged the compact nature of this library to systematically screen SARS-CoV-2 at two physiologically relevant temperatures along with three related coronaviruses (human coronavirus 229E [HCoV-229E], HCoV-NL63, and HCoV-OC43), allowing us to probe this interactome at a much higher resolution than genome-scale studies. This approach yielded several insights, including potential virus-specific differences in Rab GTPase requirements and glycosylphosphatidylinositol (GPI) anchor biosynthesis, as well as identification of multiple pan-coronavirus factors involved in cholesterol homeostasis. This coronavirus essentiality catalog could inform ongoing drug development efforts aimed at intercepting and treating coronavirus disease 2019 (COVID-19) and help prepare for future coronavirus outbreaks. 
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