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


Authors: Hoffmann, H. H.; Sánchez-Rivera, F. J.; Schneider, W. M.; Luna, J. M.; Soto-Feliciano, Y. M.; Ashbrook, A. W.; Le Pen, J.; Leal, A. A.; Ricardo-Lax, I.; Michailidis, E.; Hao, Y.; Stenzel, A. F.; Peace, A.; Zuber, J.; Allis, C. D.; Lowe, S. W.; MacDonald, M. R.; Poirier, J. T.; Rice, C. M.
Article Title: Functional interrogation of a SARS-CoV-2 host protein interactome identifies unique and shared coronavirus host factors
Abstract: Building upon a published SARS-CoV-2 protein interactome, Hoffmann et al. use a custom CRISPR library to determine which of these interacting host proteins are essential for infection by SARS-CoV-2 virus as well as three seasonal coronaviruses. These factors represent potential targets to combat COVID-19 and perhaps future coronavirus outbreaks. © 2020 Elsevier Inc. 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. © 2020 Elsevier Inc.
Keywords: coronavirus; crispr; covid-19; sars-cov-2; hcov; hcov-229e; hcov-nl63; hcov-oc43; virus-host interactome
Journal Title: Cell Host & Microbe
Volume: 29
Issue: 2
ISSN: 1931-3128
Publisher: Cell Press  
Date Published: 2021-02-10
Start Page: 267
End Page: 280.e5
Language: English
DOI: 10.1016/j.chom.2020.12.009
PUBMED: 33357464
PROVIDER: scopus
PMCID: PMC7833927
DOI/URL:
Notes: Article -- Export Date: 1 March 2021 -- Source: Scopus
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  1. Scott W Lowe
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