The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses

Antiviral Res. 2024 Apr:224:105837. doi: 10.1016/j.antiviral.2024.105837. Epub 2024 Feb 20.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • COVID-19*
  • Dystroglycans
  • Escherichia coli
  • Humans
  • Mice
  • Mice, Transgenic
  • Pandemics
  • SARS-CoV-2*

Substances

  • Dystroglycans
  • Antiviral Agents