| First Author | Zhuang X | Year | 2021 |
| Journal | bioRxiv | PubMed ID | 33758862 |
| Mgi Jnum | J:303203 | Mgi Id | MGI:6512357 |
| Doi | 10.1101/2021.03.20.436163 | Citation | Zhuang X, et al. (2021) The circadian clock component BMAL1 regulates SARS-CoV-2 entry and replication in lung epithelial cells. bioRxiv |
| abstractText | The COVID-19 pandemic, caused by SARS-CoV-2 coronavirus, is a global health issue with unprecedented challenges for public health. SARS-CoV-2 primarily infects cells of the respiratory tract, via Spike glycoprotein binding angiotensin-converting enzyme (ACE2). Circadian rhythms coordinate an organismaeuros response to its environment and can regulate host susceptibility to virus infection. We demonstrate a circadian regulation of ACE2 in lung epithelial cells and show that silencing BMAL1 or treatment with a synthetic REV-ERB agonist SR9009 reduces ACE2 expression and inhibits SARS-CoV-2 entry. Treating infected cells with SR9009 limits viral replication and secretion of infectious particles, showing that post-entry steps in the viral life cycle are influenced by the circadian system. Transcriptome analysis revealed that Bmal1 silencing induced a wide spectrum of interferon stimulated genes in Calu-3 lung epithelial cells, providing a mechanism for the circadian pathway to dampen SARS-CoV-2 infection. Our study suggests new approaches to understand and improve therapeutic targeting of SARS-CoV-2. |
