Journal
CELL REPORTS
Volume 35, Issue 3, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109020
Keywords
-
Categories
Funding
- Wellcome Investigator Award (IA) [200838/Z/16/Z]
- UK Medical Research Council (MRC) project [MR/R022011/1]
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China [2018-I2M-2-002]
- Oxford Branch of the Ludwig Institute for Cancer Research
- Wellcome IA [106241/Z/14/Z, 209412/Z/17/Z]
- Francis Crick Institute from Cancer Research UK [FC001501]
- UK MRC [FC001501]
- Paradifference Foundation
- COVID-19 Research Response Fund, University of Oxford
- Clarendon scholarships fund
- Christopher Welch Trust
- Medial Sciences Graduate Studentship, University of Oxford
- National Institute for Health Research (NIHR) Oxford Biomedical Research Centre
- Wellcome [FC001501, 104553/z/14/z, 211050/Z/18/z, 091911/B/10/Z]
- Wellcome Trust [211050/Z/18/Z, 209412/Z/17/Z, 106241/Z/14/Z, 200838/Z/16/Z, 104553/Z/14/Z] Funding Source: Wellcome Trust
Ask authors/readers for more resources
COVID-19, caused by the novel coronavirus SARS-CoV-2, has resulted in over 2 million fatalities worldwide. This study demonstrates that hypoxia and the HIF prolyl hydroxylase inhibitor Roxadustat can reduce ACE2 expression, inhibiting SARS-CoV-2 entry and replication in lung epithelial cells through an HIF-1a-dependent pathway. This research suggests the potential use of HIF prolyl hydroxylase inhibitors in preventing or treating COVID-19 by targeting the oxygen sensitivity of post-entry viral life cycle steps.
COVID-19, caused by the novel coronavirus SARS-CoV-2, is a global health issue with more than 2 million fatalities to date. Viral replication is shaped by the cellular microenvironment, and one important factor to consider is oxygen tension, in which hypoxia inducible factor (HIF) regulates transcriptional responses to hypoxia. SARS-CoV-2 primarily infects cells of the respiratory tract, entering via its spike glycoprotein binding to angiotensin-converting enzyme 2 (ACE2). We demonstrate that hypoxia and the HIF prolyl hydroxylase inhibitor Roxadustat reduce ACE2 expression and inhibit SARS-CoV-2 entry and replication in lung epithelial cells via an HIF-1a-dependent pathway. Hypoxia and Roxadustat inhibit SARS-CoV-2 RNA replication, showing that post-entry steps in the viral life cycle are oxygen sensitive. This study highlights the importance of HIF signaling in regulating multiple aspects of SARS-CoV-2 infection and raises the potential use of HIF prolyl hydroxylase inhibitors in the prevention or treatment of COVID-19.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available