tetano
Editor, Senior Moderator
Antiviral Res
. 2024 Feb 20:105837.
doi: 10.1016/j.antiviral.2024.105837. Online ahead of print. The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses
Maria Giulia Bigotti[SUP] 1 [/SUP], Katja Klein[SUP] 2 [/SUP], Esther S Gan[SUP] 3 [/SUP], Maria Anastasina[SUP] 4 [/SUP], Simon Andersson[SUP] 5 [/SUP], Olli Vapalahti[SUP] 6 [/SUP], Pekka Katajisto[SUP] 7 [/SUP], Maximilian Erdmann[SUP] 8 [/SUP], Andrew D Davidson[SUP] 8 [/SUP], Sarah J Butcher[SUP] 4 [/SUP], Ian Collinson[SUP] 9 [/SUP], Eng Eong Ooi[SUP] 10 [/SUP], Giuseppe Balistreri[SUP] 11 [/SUP], Andrea Brancaccio[SUP] 12 [/SUP], Yohei Yamauchi[SUP] 13 [/SUP]
Affiliations
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.
Keywords: Broad-range antiviral; Coronaviruses; Enveloped viruses; Extracellular matrix; SARS-CoV-2; α-dystroglycan.
. 2024 Feb 20:105837.
doi: 10.1016/j.antiviral.2024.105837. Online ahead of print. The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses
Maria Giulia Bigotti[SUP] 1 [/SUP], Katja Klein[SUP] 2 [/SUP], Esther S Gan[SUP] 3 [/SUP], Maria Anastasina[SUP] 4 [/SUP], Simon Andersson[SUP] 5 [/SUP], Olli Vapalahti[SUP] 6 [/SUP], Pekka Katajisto[SUP] 7 [/SUP], Maximilian Erdmann[SUP] 8 [/SUP], Andrew D Davidson[SUP] 8 [/SUP], Sarah J Butcher[SUP] 4 [/SUP], Ian Collinson[SUP] 9 [/SUP], Eng Eong Ooi[SUP] 10 [/SUP], Giuseppe Balistreri[SUP] 11 [/SUP], Andrea Brancaccio[SUP] 12 [/SUP], Yohei Yamauchi[SUP] 13 [/SUP]
Affiliations
- PMID: 38387750
- DOI: 10.1016/j.antiviral.2024.105837
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.
Keywords: Broad-range antiviral; Coronaviruses; Enveloped viruses; Extracellular matrix; SARS-CoV-2; α-dystroglycan.