2. Academic Validation
  3. Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks

Genome-Scale Identification of SARS-CoV-2 and Pan-coronavirus Host Factor Networks

  • Cell. 2021 Jan 7;184(1):120-132.e14. doi: 10.1016/j.cell.2020.12.006.
William M Schneider 1,  Joseph M Luna 1,  H-Heinrich Hoffmann 1,  Francisco J Sánchez-Rivera 2,  Andrew A Leal 3,  Alison W Ashbrook 1,  Jérémie Le Pen 1,  Inna Ricardo-Lax 1,  Eleftherios Michailidis 1,  Avery Peace 1,  Ansgar F Stenzel 4,  Scott W Lowe 2,  Margaret R MacDonald 1,  Charles M Rice 5,  John T Poirier 6
Affiliations

Affiliations

  • 1 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
  • 2 Cancer Biology and Genetics, MSKCC, New York, NY 10065, USA.
  • 3 Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016, USA.
  • 4 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA; Department of Infectious Diseases, Molecular Virology, Heidelberg University, Heidelberg, Germany.
  • 5 Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA. Electronic address: ricec@rockefeller.edu.
  • 6 Laura and Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, NYU Langone Health, New York, NY 10016, USA. Electronic address: john.poirier@nyulangone.org.
PMID: 33382968 DOI: 10.1016/j.cell.2020.12.006
Abstract

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.

Keywords

COVID-19; CRISPR; HCoV-229E; HCoV-NL63; HCoV-OC43; SARS-CoV-2; TMEM41B; coronavirus; genetic screens; host factors.

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