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

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.

• Authors: Geng Liu, Wenya Du, Xiongbo Sang, Qiyu Tong, Ye Wang, Guoqing Chen, Yi Yuan, Lili Jiang, Wei Cheng, Dan Liu, Yan Tian, Xianghui Fu
• Journal: Nature communications (Nat Commun) Vol. 13 Issue 1 Pg. 1444 (03 17 2022) ISSN: 2041-1723 [Electronic] England
• PMID: 35301316 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2022. The Author(s).

Chemical References

• RNA
• Serine Endopeptidases
• TMPRSS2 protein, human

Topics

• Animals
• COVID-19
• Humans
• Mice
• RNA
• SARS-CoV-2
• Serine Endopeptidases (genetics)
• Virus Internalization