The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses.
JSON
Bigotti MG, Klein K, Gan ES, Anastasina M, Andersson S, Vapalahti O, Katajisto P, Erdmann M, Davidson AD, Butcher SJ, Collinson I, Ooi EE, Balistreri G, Brancaccio A, Yamauchi Y
Antiviral Res 224 (-) 105837 [2024-02-20; online 2024-02-20]
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.
PubMed 38387750
DOI 10.1016/j.antiviral.2024.105837
Crossref 10.1016/j.antiviral.2024.105837
pii: S0166-3542(24)00045-7