Genetic Screens Identify Host Factors for SARS-CoV-2 and Common Cold Coronaviruses.

Ruofan WangAndreas S Puschnik


The Coronaviridae are a family of viruses that cause disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted genome-wide CRISPR screens in cells infected by SARS-CoV-2 as well as two seasonally circulating common cold coronaviruses, OC43 and 229E. This approach correctly identified the distinct viral entry factors ACE2 (for SARS-CoV-2), aminopeptidase N (for 229E), and glycosaminoglycans (for OC43). Additionally, we identified phosphatidylinositol phosphate biosynthesis and cholesterol homeostasis as critical host pathways supporting infection by all three coronaviruses. By contrast, the lysosomal protein TMEM106B appeared unique to SARS-CoV-2 infection. Pharmacological inhibition of phosphatidylinositol kinases and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle and the development of host-directed therapies.


Mar 22, 2003·RNA·Sheila A StewartCarl D Novina
Apr 12, 2003·The New England Journal of Medicine·Christian DrostenHans Wilhelm Doerr
Nov 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Takahiko Matsuda, Constance L Cepko
Mar 30, 2004·The Journal of Biological Chemistry·Yohei KatohKazuhisa Nakayama
May 18, 2005·Proceedings of the National Academy of Sciences of the United States of America·Heike HofmannStefan Pöhlmann
Jun 9, 2005·Proceedings of the National Academy of Sciences of the United States of America·Jin ZhongFrancis V Chisari
Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Jun 26, 2007·Nature·Gian Maria FimiaFrancesco Cecconi
Sep 17, 2008·Nature Cell Biology·Yusuke MaedaTaroh Kinoshita
Aug 13, 2009·Nature Reviews. Molecular Cell Biology·Paul Saftig, Judith Klumperman
Sep 1, 2009·Chemistry & Biology·Shinji KamisukiMotonari Uesugi
Nov 13, 2010·Nucleic Acids Research·Ethan G CeramiChris Sander
Nov 26, 2010·Nature·Cory M JohannessenLevi A Garraway
Dec 3, 2010·Bioinformatics·Gang SuFan Meng
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Yueguang RongMichael J Lenardo
Aug 10, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kevin T BeierConstance L Cepko
Aug 26, 2011·Nature·Jan E CaretteThijn R Brummelkamp
Oct 19, 2012·The New England Journal of Medicine·Ali M ZakiRon A M Fouchier
May 7, 2013·Journal of Cell Science·Henning J kleine Balderhaar, Christian Ungermann
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Feb 12, 2014·PLoS Pathogens·Josiah PetersenKenneth Briley
Feb 21, 2014·Molecular Biology of the Cell·Peidu JiangNoboru Mizushima
Jul 31, 2014·Nature Methods·Neville E SanjanaFeng Zhang
Oct 20, 2014·Nature Chemical Biology·Baptiste RonanBenoit Pasquier
Apr 18, 2015·Science·Elena Bekerman, Shirit Einav
Nov 3, 2014·Annual Review of Virology·Luisa J Ströh, Thilo Stehle
Aug 26, 2016·Molecular Biology of the Cell·Krisztina HegedűsGábor Juhász
Apr 20, 2017·Nature Reviews. Microbiology·Andreas S PuschnikJan E Carette
Jun 14, 2017·Nature Reviews. Genetics·Lenore CowenRoded Sharan
Aug 26, 2017·Annual Review of Biochemistry·Michael S BrownJoseph L Goldstein
May 16, 2018·G3 : Genes - Genomes - Genetics·Sarah EdieRoger H Reeves
Aug 22, 2018·EMBO Reports·Francesca MorettiBeat Nyfeler
Sep 12, 2018·Current Biology : CB·Kunrong Mei, Wei Guo

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