RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection

Geng Liu, Wenya Du, Xiongbo Sang, Qiyu Tong, Ye Wang, Guoqing Chen, Yi Yuan, Lili Jiang, Wei Cheng, Dan Liu, Yan Tian and Xianghui Fu ()
Additional contact information
Geng Liu: Sichuan University and Collaborative Innovation Center of Biotherapy
Wenya Du: Sichuan University and Collaborative Innovation Center of Biotherapy
Xiongbo Sang: Sichuan University and Collaborative Innovation Center of Biotherapy
Qiyu Tong: Sichuan University and Collaborative Innovation Center of Biotherapy
Ye Wang: Division of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University
Guoqing Chen: Sichuan University
Yi Yuan: Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences
Lili Jiang: Lab of Pathology, West China Hospital, Sichuan University
Wei Cheng: Sichuan University
Dan Liu: Division of Pulmonary and Critical Care Medicine, West China Hospital, Sichuan University
Yan Tian: Sichuan University and Collaborative Innovation Center of Biotherapy
Xianghui Fu: Sichuan University and Collaborative Innovation Center of Biotherapy

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to have devastating consequences worldwide. Recently, great efforts have been made to identify SARS-CoV-2 host factors, but the regulatory mechanisms of these host molecules, as well as the virus per se, remain elusive. Here we report a role of RNA G-quadruplex (RG4) in SARS-CoV-2 infection. Combining bioinformatics, biochemical and biophysical assays, we demonstrate the presence of RG4s in both SARS-CoV-2 genome and host factors. The biological and pathological importance of these RG4s is then exemplified by a canonical 3-quartet RG4 within Tmprss2, which can inhibit Tmprss2 translation and prevent SARS-CoV-2 entry. Intriguingly, G-quadruplex (G4)-specific stabilizers attenuate SARS-CoV-2 infection in pseudovirus cell systems and mouse models. Consistently, the protein level of TMPRSS2 is increased in lungs of COVID-19 patients. Our findings reveal a previously unknown mechanism underlying SARS-CoV-2 infection and suggest RG4 as a potential target for COVID-19 prevention and treatment.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-29135-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29135-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-29135-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().