tetano
Editor, Senior Moderator
Nat Commun
. 2022 Mar 17;13(1):1444.
doi: 10.1038/s41467-022-29135-5.
RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
Geng Liu[SUP] #[/SUP][SUP] 1 [/SUP], Wenya Du[SUP] #[/SUP][SUP] 1 [/SUP], Xiongbo Sang[SUP] 1 [/SUP], Qiyu Tong[SUP] 1 [/SUP], Ye Wang[SUP] 2 [/SUP], Guoqing Chen[SUP] 3 [/SUP], Yi Yuan[SUP] 4 [/SUP], Lili Jiang[SUP] 5 [/SUP], Wei Cheng[SUP] 3 [/SUP], Dan Liu[SUP] 2 [/SUP], Yan Tian[SUP] 1 [/SUP], Xianghui Fu[SUP] 6 [/SUP]
Affiliations
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.
. 2022 Mar 17;13(1):1444.
doi: 10.1038/s41467-022-29135-5.
RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection
Geng Liu[SUP] #[/SUP][SUP] 1 [/SUP], Wenya Du[SUP] #[/SUP][SUP] 1 [/SUP], Xiongbo Sang[SUP] 1 [/SUP], Qiyu Tong[SUP] 1 [/SUP], Ye Wang[SUP] 2 [/SUP], Guoqing Chen[SUP] 3 [/SUP], Yi Yuan[SUP] 4 [/SUP], Lili Jiang[SUP] 5 [/SUP], Wei Cheng[SUP] 3 [/SUP], Dan Liu[SUP] 2 [/SUP], Yan Tian[SUP] 1 [/SUP], Xianghui Fu[SUP] 6 [/SUP]
Affiliations
- PMID: 35301316
- DOI: 10.1038/s41467-022-29135-5
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.