Competitive cleavage of SARS-CoV-2 spike protein and epithelial sodium channel by plasmin as a potential mechanism for COVID-19 infection
Cleavage of the furin site in SARS-CoV-2 spike (S) protein accounts for increased transmissibility of COVID-19 by promoting the entry of virus into host cells through specific angiotensin-converting enzyme 2 (ACE2) receptors. Plasmin, a key serine protease of fibrinolysis system, cleaves the furin site of γ subunit of human epithelial sodium channels (ENaCs). Sharing the plasmin cleavage by viral S and host ENaC proteins may competitively inter-regulate SARS-CoV-2 transmissibility and edema resolution via the ENaC pathway. To address this possibility, we analyzed single-cell RNA sequence (scRNA-seq) data sets and found that PLAU (encoding urokinase plasminogen activator), SCNN1G (γENaC), and ACE2 (SARS-CoV-2 receptor) were co-expressed in airway/alveolar epithelial cells. The expression levels of PLAU and FURIN were significantly higher compared with TMPRSS2 in healthy group. This difference was further amplified in both epithelial and immune cells in patients with moderate/severe COVID-19 and SARS-CoV-2 infected airway/alveolar epithelial cell lines. Of note, plasmin cleaved the S protein and facilitated the entry of pseudovirus in HEK293 cells. Conclusively, SARS-CoV-2 may expedite infusion by competing the fibrinolytic protease network with ENaC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:323 |
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| Enthalten in: |
American journal of physiology. Lung cellular and molecular physiology - 323(2022), 5 vom: 01. Nov., Seite L569-L577 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hou, Yapeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.11.2022 Date Revised 14.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1152/ajplung.00152.2022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Competitive cleavage of SARS-CoV-2 spike protein and epithelial sodium channel by plasmin as a potential mechanism for COVID-19 infection |
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| 520 | |a Cleavage of the furin site in SARS-CoV-2 spike (S) protein accounts for increased transmissibility of COVID-19 by promoting the entry of virus into host cells through specific angiotensin-converting enzyme 2 (ACE2) receptors. Plasmin, a key serine protease of fibrinolysis system, cleaves the furin site of γ subunit of human epithelial sodium channels (ENaCs). Sharing the plasmin cleavage by viral S and host ENaC proteins may competitively inter-regulate SARS-CoV-2 transmissibility and edema resolution via the ENaC pathway. To address this possibility, we analyzed single-cell RNA sequence (scRNA-seq) data sets and found that PLAU (encoding urokinase plasminogen activator), SCNN1G (γENaC), and ACE2 (SARS-CoV-2 receptor) were co-expressed in airway/alveolar epithelial cells. The expression levels of PLAU and FURIN were significantly higher compared with TMPRSS2 in healthy group. This difference was further amplified in both epithelial and immune cells in patients with moderate/severe COVID-19 and SARS-CoV-2 infected airway/alveolar epithelial cell lines. Of note, plasmin cleaved the S protein and facilitated the entry of pseudovirus in HEK293 cells. Conclusively, SARS-CoV-2 may expedite infusion by competing the fibrinolytic protease network with ENaC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a epithelial sodium channels | |
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| 650 | 4 | |a plasmin | |
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| 700 | 1 | |a Yu, Tong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Tingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Nie, Hongguang |e verfasserin |4 aut | |
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