Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets

View ORCID ProfileAnnika Kratzel, Jenna N. Kelly, Yannick Brueggemann, Jasmine Portmann, Philip V’kovski, Daniel Todt, Nadine Ebert, Eike Steinmann, View ORCID ProfileRonald Dijkman, Gert Zimmer, Stephanie Pfaender, Volker Thiel
doi: https://doi.org/10.1101/2021.02.24.432634
Annika Kratzel
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
3Graduate School for Biomedical Science, University of Bern, Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Annika Kratzel
Jenna N. Kelly
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
6European Virus Bioinformatics Center (EVBC), Jena, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yannick Brueggemann
4Department for Molecular & Medical Virology, Ruhr-Universität Bochum, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jasmine Portmann
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Philip V’kovski
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel Todt
4Department for Molecular & Medical Virology, Ruhr-Universität Bochum, Germany
6European Virus Bioinformatics Center (EVBC), Jena, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nadine Ebert
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eike Steinmann
4Department for Molecular & Medical Virology, Ruhr-Universität Bochum, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronald Dijkman
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
5Institute for Infectious Diseases, University of Bern, Bern, Switzerland
6European Virus Bioinformatics Center (EVBC), Jena, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Ronald Dijkman
Gert Zimmer
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Stephanie Pfaender
4Department for Molecular & Medical Virology, Ruhr-Universität Bochum, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Volker.thiel@vetsuisse.unibe.ch stephanie.pfaender@ruhr-uni-bochum.de
Volker Thiel
1Institute of Virology and Immunology, Bern and Mittelhäusern, Switzerland
2Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Volker.thiel@vetsuisse.unibe.ch stephanie.pfaender@ruhr-uni-bochum.de
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Summary

Over the past 20 years, the emergence of three highly pathogenic coronaviruses (CoV) – SARS-CoV, MERS-CoV, and most recently SARS-CoV-2 – has shown that CoVs pose a serious risk to human health and highlighted the importance of developing effective therapies against them. Similar to other viruses, CoVs are dependent on host factors for their survival and replication. We hypothesized that evolutionarily distinct CoVs may exploit similar host factors and pathways to support their replication cycle. Here, we conducted two independent genome-wide CRISPR/Cas9 knockout screens to identify pan-CoV host factors required for the replication of both endemic and emerging CoVs, including the novel CoV SARS-CoV-2. Strikingly, we found that several autophagy-related genes, including the immunophilin FKBP8, TMEM41B, and MINAR1, were common host factors required for CoV replication. Importantly, inhibition of the immunophilin family with the compounds Tacrolimus, Cyclosporin A, and the non-immunosuppressive derivative Alisporivir, resulted in dose-dependent inhibition of CoV replication in primary human nasal epithelial cell cultures that resemble the natural site of virus replication. Overall, we identified host factors that are crucial for CoV replication and demonstrate that these factors constitute potential targets for therapeutic intervention by clinically approved drugs.

Competing Interest Statement

The authors have declared no competing interest.

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-ND 4.0 International license.
Back to top
PreviousNext
Posted February 24, 2021.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets
Annika Kratzel, Jenna N. Kelly, Yannick Brueggemann, Jasmine Portmann, Philip V’kovski, Daniel Todt, Nadine Ebert, Eike Steinmann, Ronald Dijkman, Gert Zimmer, Stephanie Pfaender, Volker Thiel
bioRxiv 2021.02.24.432634; doi: https://doi.org/10.1101/2021.02.24.432634
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
A genome-wide CRISPR screen identifies interactors of the autophagy pathway as conserved coronavirus targets
Annika Kratzel, Jenna N. Kelly, Yannick Brueggemann, Jasmine Portmann, Philip V’kovski, Daniel Todt, Nadine Ebert, Eike Steinmann, Ronald Dijkman, Gert Zimmer, Stephanie Pfaender, Volker Thiel
bioRxiv 2021.02.24.432634; doi: https://doi.org/10.1101/2021.02.24.432634

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4382)
  • Biochemistry (9591)
  • Bioengineering (7090)
  • Bioinformatics (24856)
  • Biophysics (12600)
  • Cancer Biology (9956)
  • Cell Biology (14349)
  • Clinical Trials (138)
  • Developmental Biology (7948)
  • Ecology (12105)
  • Epidemiology (2067)
  • Evolutionary Biology (15988)
  • Genetics (10925)
  • Genomics (14738)
  • Immunology (9869)
  • Microbiology (23659)
  • Molecular Biology (9484)
  • Neuroscience (50856)
  • Paleontology (369)
  • Pathology (1539)
  • Pharmacology and Toxicology (2681)
  • Physiology (4013)
  • Plant Biology (8657)
  • Scientific Communication and Education (1508)
  • Synthetic Biology (2394)
  • Systems Biology (6433)
  • Zoology (1346)