Conserved requirement of autophagy-related effectors during coronavirus replication

Yannick Brüggemann; Annika Kratzel; Lea Almeida; Jenna N Kelly; Volker Thiel; Stephanie Pfaender

doi:10.1080/15548627.2022.2100617

Conserved requirement of autophagy-related effectors during coronavirus replication

Autophagy. 2023 Feb;19(2):731-733. doi: 10.1080/15548627.2022.2100617. Epub 2022 Jul 24.

Authors

Yannick Brüggemann¹, Annika Kratzel^{2

3

4}, Lea Almeida^{2

3

4}, Jenna N Kelly^{2

3

5

6}, Volker Thiel^{2

3

5

6}, Stephanie Pfaender¹

Affiliations

¹ Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.
² Institute of Virology and Immunology (IVI), Bern, Switzerland.
³ Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
⁴ Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
⁵ European Virus Bioinformatics Center, Jena, Germany.
⁶ Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland.

Abstract

The recurrence of zoonotic transmission events highlights the need for novel treatment strategies against emerging coronaviruses (CoVs), namely SARS-CoV, MERS-CoV and most notably SARS-CoV-2. Our recently performed genome-wide CRISPR knockout screen revealed a list of conserved pan-coronavirus as well as MERS-CoV or HCoV-229E-specific host dependency factors (HDF) essential during the viral life cycle. Intriguingly, we identified the macroautophagy/autophagy pathway-regulating immunophilins FKBP8, TMEM41B, and MINAR1 as conserved MERS-CoV, HCoV-229E, SARS-CoV, and SARS-CoV-2 host factors, which further constitute potential targets for therapeutic intervention by clinically approved drugs.

Keywords: Antiviral target; CRISPR screen; autophagy; coronavirus; host factor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autophagy*
COVID-19
Coronavirus 229E, Human
Host-Derived Cellular Factors*
Humans
Immunophilins*
Middle East Respiratory Syndrome Coronavirus
SARS-CoV-2
Severe acute respiratory syndrome-related coronavirus
Virus Replication*

Substances

Immunophilins
Host-Derived Cellular Factors

Grants and funding

This study was supported by the Swiss National Science Foundation (grant number 165076 and 173085, VT) and the German Ministry of Education and Research (BMBF; RAPID, VT)