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

Author

Listed:
  • 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)

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.

Suggested Citation

  • Geng Liu & Wenya Du & Xiongbo Sang & Qiyu Tong & Ye Wang & Guoqing Chen & Yi Yuan & Lili Jiang & Wei Cheng & Dan Liu & Yan Tian & Xianghui Fu, 2022. "RNA G-quadruplex in TMPRSS2 reduces SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29135-5
    DOI: 10.1038/s41467-022-29135-5
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    1. Bo Qin & Ziheng Li & Kaiming Tang & Tongyun Wang & Yubin Xie & Sylvain Aumonier & Meitian Wang & Shuofeng Yuan & Sheng Cui, 2023. "Identification of the SARS-unique domain of SARS-CoV-2 as an antiviral target," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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