The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses
Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved..
The COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on α-dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of α-dystroglycan (α-DGN), as produced in E. coli in the absence of post-translational modifications, blocks infection of SARS-CoV-2 in cell culture, human primary gut organoids and the lungs of transgenic mice expressing the human receptor angiotensin I-converting enzyme 2 (hACE2). Prophylactic and therapeutic administration of α-DGN reduced SARS-CoV-2 lung titres and protected the mice from respiratory symptoms and death. Recombinant α-DGN also blocked infection of a wide range of enveloped viruses including the four Dengue virus serotypes, influenza A virus, respiratory syncytial virus, tick-borne encephalitis virus, but not human adenovirus, a non-enveloped virus in vitro. This study establishes soluble recombinant α-DGN as a broad-band, natural compound candidate therapeutic against enveloped viruses.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:224 |
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| Enthalten in: |
Antiviral research - 224(2024) vom: 20. März, Seite 105837 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bigotti, Maria Giulia [VerfasserIn] |
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| Links: |
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| Themen: |
α-dystroglycan |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 18.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.antiviral.2024.105837 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368777375 |
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| 245 | 1 | 4 | |a The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses |
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| 520 | |a The COVID-19 pandemic has shown the need to develop effective therapeutics in preparedness for further epidemics of virus infections that pose a significant threat to human health. As a natural compound antiviral candidate, we focused on α-dystroglycan, a highly glycosylated basement membrane protein that links the extracellular matrix to the intracellular cytoskeleton. Here we show that the N-terminal fragment of α-dystroglycan (α-DGN), as produced in E. coli in the absence of post-translational modifications, blocks infection of SARS-CoV-2 in cell culture, human primary gut organoids and the lungs of transgenic mice expressing the human receptor angiotensin I-converting enzyme 2 (hACE2). Prophylactic and therapeutic administration of α-DGN reduced SARS-CoV-2 lung titres and protected the mice from respiratory symptoms and death. Recombinant α-DGN also blocked infection of a wide range of enveloped viruses including the four Dengue virus serotypes, influenza A virus, respiratory syncytial virus, tick-borne encephalitis virus, but not human adenovirus, a non-enveloped virus in vitro. This study establishes soluble recombinant α-DGN as a broad-band, natural compound candidate therapeutic against enveloped viruses | ||
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| 700 | 1 | |a Gan, Esther S |e verfasserin |4 aut | |
| 700 | 1 | |a Anastasina, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Andersson, Simon |e verfasserin |4 aut | |
| 700 | 1 | |a Vapalahti, Olli |e verfasserin |4 aut | |
| 700 | 1 | |a Katajisto, Pekka |e verfasserin |4 aut | |
| 700 | 1 | |a Erdmann, Maximilian |e verfasserin |4 aut | |
| 700 | 1 | |a Davidson, Andrew D |e verfasserin |4 aut | |
| 700 | 1 | |a Butcher, Sarah J |e verfasserin |4 aut | |
| 700 | 1 | |a Collinson, Ian |e verfasserin |4 aut | |
| 700 | 1 | |a Ooi, Eng Eong |e verfasserin |4 aut | |
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| 700 | 1 | |a Brancaccio, Andrea |e verfasserin |4 aut | |
| 700 | 1 | |a Yamauchi, Yohei |e verfasserin |4 aut | |
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