TY - JOUR T1 - Functional genomic screens identify human host factors for SARS-CoV-2 and common cold coronaviruses JF - bioRxiv DO - 10.1101/2020.09.24.312298 SP - 2020.09.24.312298 AU - Ruofan Wang AU - Camille R. Simoneau AU - Jessie Kulsuptrakul AU - Mehdi Bouhaddou AU - Katherine Travisano AU - Jennifer M. Hayashi AU - Jared Carlson-Stevermer AU - Jennifer Oki AU - Kevin Holden AU - Nevan J. Krogan AU - Melanie Ott AU - Andreas S. Puschnik Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/09/24/2020.09.24.312298.abstract N2 - The Coronaviridae are a family of viruses that causes disease in humans ranging from mild respiratory infection to potentially lethal acute respiratory distress syndrome. Finding host factors that are common to multiple coronaviruses could facilitate the development of therapies to combat current and future coronavirus pandemics. Here, we conducted parallel 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 discovered 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 phosphate biosynthesis and cholesterol homeostasis reduced replication of all three coronaviruses. These findings offer important insights for the understanding of the coronavirus life cycle as well as the potential development of host-directed therapies.Competing Interest StatementJ.C.S., J.O. and K.H. are employees of Synthego Corporation. ER -