• 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.
• Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
• Cell Host Microbe. 2021 Feb 10; 29 (2): 267-280.e5.

AbstractThe 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.Copyright © 2020 Elsevier Inc. All rights reserved.

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