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Genome-scale CRISPR Screens Identify Host Factors that Promote Human Coronavirus Infection

Marco Grodzki, Andrew P. Bluhm, Moritz Schäfer, Abderrahmane Tagmount, Max Russo, Amin Sobh, Roya Rafiee, Chris D. Vulpe, Stephanie M. Karst, Michael H. Norris
doi: https://doi.org/10.1101/2021.06.04.447090
Marco Grodzki
1Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida; Gainesville, Florida, United States of America
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Andrew P. Bluhm
2Department of Geography, College of Liberal Arts and Sciences, University of Florida; Gainesville, Florida, United States of America
3Emerging Pathogens Institute, University of Florida; Gainesville, Florida, United States of America
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Moritz Schäfer
4Institute for Molecular Health Sciences, Swiss Federal Institute of Technology in Zürich; Zurich, Switzerland
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Abderrahmane Tagmount
5Department of Physiological Sciences, College of Veterinary Medicine, University of Florida; Gainesville, Florida, United States of America
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Max Russo
5Department of Physiological Sciences, College of Veterinary Medicine, University of Florida; Gainesville, Florida, United States of America
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Amin Sobh
6Univeristy of Florida Heath Cancer Center, University of Florida; Gainesville, Florida, United States of America
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Roya Rafiee
7Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida; Gainesville, Florida, United States of America
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Chris D. Vulpe
5Department of Physiological Sciences, College of Veterinary Medicine, University of Florida; Gainesville, Florida, United States of America
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Stephanie M. Karst
1Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida; Gainesville, Florida, United States of America
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  • For correspondence: skarst@ufl.edu mhnorris@ufl.edu
Michael H. Norris
2Department of Geography, College of Liberal Arts and Sciences, University of Florida; Gainesville, Florida, United States of America
3Emerging Pathogens Institute, University of Florida; Gainesville, Florida, United States of America
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  • For correspondence: skarst@ufl.edu mhnorris@ufl.edu
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Abstract

The COVID-19 pandemic has resulted in 153 million infections and 3.2 million deaths as of May 2021. While effective vaccines are being administered globally, there is still a great need for antiviral therapies as potentially antigenically distinct SARS-CoV-2 variants continue to emerge across the globe. Viruses require host factors at every step in their life cycle, representing a rich pool of candidate targets for antiviral drug design. To identify host factors that promote SARS-CoV-2 infection with potential for broad-spectrum activity across the coronavirus family, we performed genome-scale CRISPR knockout screens in two cell lines (Vero E6 and HEK293T ectopically expressing ACE2) with SARS-CoV-2 and the common cold-causing human coronavirus OC43. While we identified multiple genes and functional pathways that have been previously reported to promote human coronavirus replication, we also identified a substantial number of novel genes and pathways. Of note, host factors involved in cell cycle regulation were enriched in our screens as were several key components of the programmed mRNA decay pathway. Finally, we identified novel candidate antiviral compounds targeting a number of factors revealed by our screens. Overall, our studies substantiate and expand the growing body of literature focused on understanding key human coronavirus-host cell interactions and exploit that knowledge for rational antiviral drug development.

One Sentence Summary Genome-wide CRISPR screens identified host factors that promote human coronavirus infection, revealing novel antiviral drug targets.

Competing Interest Statement

A patent entitled Methods of Treatment for SARS-CoV-2 Infections (PROV Appl. No. 63/145,763) was filed on February 4, 2021.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted June 04, 2021.
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Genome-scale CRISPR Screens Identify Host Factors that Promote Human Coronavirus Infection
Marco Grodzki, Andrew P. Bluhm, Moritz Schäfer, Abderrahmane Tagmount, Max Russo, Amin Sobh, Roya Rafiee, Chris D. Vulpe, Stephanie M. Karst, Michael H. Norris
bioRxiv 2021.06.04.447090; doi: https://doi.org/10.1101/2021.06.04.447090
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Genome-scale CRISPR Screens Identify Host Factors that Promote Human Coronavirus Infection
Marco Grodzki, Andrew P. Bluhm, Moritz Schäfer, Abderrahmane Tagmount, Max Russo, Amin Sobh, Roya Rafiee, Chris D. Vulpe, Stephanie M. Karst, Michael H. Norris
bioRxiv 2021.06.04.447090; doi: https://doi.org/10.1101/2021.06.04.447090

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