SMYD2 Inhibition Downregulates TMPRSS2 and Decreases SARS-CoV-2 Infection in Human Intestinal and Airway Epithelial Cells
The COVID-19 pandemic caused by SARS-CoV-2 has lasted for more than two years. Despite the presence of very effective vaccines, the number of virus variants that escape neutralizing antibodies is growing. Thus, there is still a need for effective antiviral treatments that target virus replication independently of the circulating variant. Here, we show for the first time that deficiency or pharmacological inhibition of the cellular lysine-methyltransferase SMYD2 decreases TMPRSS2 expression on both mRNA and protein levels. SARS-CoV-2 uses TMPRSS2 for priming its spike protein to infect target cells. Treatment of cultured cells with the SMYD2 inhibitors AZ505 or BAY598 significantly inhibited viral replication. In contrast, treatment of Vero E6 cells, which do not express detectable amounts of TMPRSS2, had no effect on SARS-CoV-2 infection. Moreover, by generating a recombinant reporter virus that expresses the spike protein of the Delta variant of SARS-CoV-2, we demonstrate that BAY598 exhibits similar antiviral activity against this variant of concern. In summary, SMYD2 inhibition downregulates TMPRSS2 and blocks viral replication. Targeting cellular SMYD2 represents a promising tool to curtail SARS-CoV-2 infection.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Cells - 11(2022), 8 vom: 08. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yu, Yu-Qiang [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.04.2022 Date Revised 16.07.2022 published: Electronic Citation Status MEDLINE |
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| doi: |
10.3390/cells11081262 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM339851112 |
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| 100 | 1 | |a Yu, Yu-Qiang |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SMYD2 Inhibition Downregulates TMPRSS2 and Decreases SARS-CoV-2 Infection in Human Intestinal and Airway Epithelial Cells |
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| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The COVID-19 pandemic caused by SARS-CoV-2 has lasted for more than two years. Despite the presence of very effective vaccines, the number of virus variants that escape neutralizing antibodies is growing. Thus, there is still a need for effective antiviral treatments that target virus replication independently of the circulating variant. Here, we show for the first time that deficiency or pharmacological inhibition of the cellular lysine-methyltransferase SMYD2 decreases TMPRSS2 expression on both mRNA and protein levels. SARS-CoV-2 uses TMPRSS2 for priming its spike protein to infect target cells. Treatment of cultured cells with the SMYD2 inhibitors AZ505 or BAY598 significantly inhibited viral replication. In contrast, treatment of Vero E6 cells, which do not express detectable amounts of TMPRSS2, had no effect on SARS-CoV-2 infection. Moreover, by generating a recombinant reporter virus that expresses the spike protein of the Delta variant of SARS-CoV-2, we demonstrate that BAY598 exhibits similar antiviral activity against this variant of concern. In summary, SMYD2 inhibition downregulates TMPRSS2 and blocks viral replication. Targeting cellular SMYD2 represents a promising tool to curtail SARS-CoV-2 infection | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 650 | 4 | |a BAY598 | |
| 650 | 4 | |a COVID-19 | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a SMYD2 | |
| 650 | 4 | |a TMPRSS2 | |
| 650 | 4 | |a antiviral treatment | |
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| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
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| 700 | 1 | |a Herrmann, Alexandra |e verfasserin |4 aut | |
| 700 | 1 | |a Thonn, Veronika |e verfasserin |4 aut | |
| 700 | 1 | |a Cordsmeier, Arne |e verfasserin |4 aut | |
| 700 | 1 | |a Neurath, Markus F |e verfasserin |4 aut | |
| 700 | 1 | |a Ensser, Armin |e verfasserin |4 aut | |
| 700 | 1 | |a Becker, Christoph |e verfasserin |4 aut | |
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