Snake venom phospholipase $ A_{2} $s exhibit strong virucidal activity against SARS-CoV-2 and inhibit the viral spike glycoprotein interaction with ACE2
Abstract The COVID-19 pandemic caused by SARS-CoV-2 requires new treatments both to alleviate the symptoms and to prevent the spread of this disease. Previous studies demonstrated good antiviral and virucidal activity of phospholipase $ A_{2} $s ($ PLA_{2} $s) from snake venoms against viruses from different families but there was no data for coronaviruses. Here we show that $ PLA_{2} $s from snake venoms protect Vero E6 cells against SARS-CoV-2 cytopathic effects. $ PLA_{2} $s showed low cytotoxicity to Vero E6 cells with some activity at micromolar concentrations, but strong antiviral activity at nanomolar concentrations. Dimeric $ PLA_{2} $ from the viper Vipera nikolskii and its subunits manifested especially potent virucidal effects, which were related to their phospholipolytic activity, and inhibited cell–cell fusion mediated by the SARS-CoV-2 spike glycoprotein. Moreover, $ PLA_{2} $s interfered with binding both of an antibody against ACE2 and of the receptor-binding domain of the glycoprotein S to 293T/ACE2 cells. This is the first demonstration of a detrimental effect of $ PLA_{2} $s on β-coronaviruses. Thus, snake $ PLA_{2} $s are promising for the development of antiviral drugs that target the viral envelope, and could also prove to be useful tools to study the interaction of viruses with host cells..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Cellular and molecular life sciences - 78(2021), 23 vom: 29. Okt., Seite 7777-7794 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Siniavin, Andrei E. [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| BKL: | |
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| Themen: |
Molecular modelling |
| Anmerkungen: |
© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2021 |
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| doi: |
10.1007/s00018-021-03985-6 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract The COVID-19 pandemic caused by SARS-CoV-2 requires new treatments both to alleviate the symptoms and to prevent the spread of this disease. Previous studies demonstrated good antiviral and virucidal activity of phospholipase $ A_{2} $s ($ PLA_{2} $s) from snake venoms against viruses from different families but there was no data for coronaviruses. Here we show that $ PLA_{2} $s from snake venoms protect Vero E6 cells against SARS-CoV-2 cytopathic effects. $ PLA_{2} $s showed low cytotoxicity to Vero E6 cells with some activity at micromolar concentrations, but strong antiviral activity at nanomolar concentrations. Dimeric $ PLA_{2} $ from the viper Vipera nikolskii and its subunits manifested especially potent virucidal effects, which were related to their phospholipolytic activity, and inhibited cell–cell fusion mediated by the SARS-CoV-2 spike glycoprotein. Moreover, $ PLA_{2} $s interfered with binding both of an antibody against ACE2 and of the receptor-binding domain of the glycoprotein S to 293T/ACE2 cells. This is the first demonstration of a detrimental effect of $ PLA_{2} $s on β-coronaviruses. Thus, snake $ PLA_{2} $s are promising for the development of antiviral drugs that target the viral envelope, and could also prove to be useful tools to study the interaction of viruses with host cells. | ||
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| 700 | 1 | |a Streltsova, Maria A. |e verfasserin |4 aut | |
| 700 | 1 | |a Nikiforova, Maria A. |e verfasserin |4 aut | |
| 700 | 1 | |a Kudryavtsev, Denis S. |e verfasserin |4 aut | |
| 700 | 1 | |a Grinkina, Svetlana D. |e verfasserin |4 aut | |
| 700 | 1 | |a Gushchin, Vladimir A. |e verfasserin |4 aut | |
| 700 | 1 | |a Mozhaeva, Vera A. |e verfasserin |4 aut | |
| 700 | 1 | |a Starkov, Vladislav G. |e verfasserin |4 aut | |
| 700 | 1 | |a Osipov, Alexey V. |e verfasserin |4 aut | |
| 700 | 1 | |a Lummis, Sarah C. R. |e verfasserin |4 aut | |
| 700 | 1 | |a Tsetlin, Victor I. |e verfasserin |4 aut | |
| 700 | 1 | |a Utkin, Yuri N. |e verfasserin |4 aut | |
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