Dystrovir – a broad spectrum anti-viral

An image of the microscopic coronavirus appearing as a grey sphere with red fluff like protrusions.

There remains a challenge for the development of broad spectrum anti-viral to treat a range of infections and novel viruses to protect populations from seasonal epidemics and in the event of future pandemics.

Technology Highlights

  1. Broad Spectrum. Proven efficacy data against SARS-CoV-2, SARS-CoV, MERS CoV, IAV, RSV, TBEV and the 4 serotypes of DENV.
  2. Low cost production and stable at room temperature.
  3. Dystrovir is based on α-DGN ,an endogenous protein fragment found in circulation, that as such is expected to be well tolerated in patients and less prone to elicit an immune response.

The Covid-19 pandemic cost the UK economy an estimated £3-4bn in public spending, with ~25M recorded infections and ~232,000 deaths. Although vaccine development has been highly successful, even the optimal speed at which this happened left the global population unprotected for over a year. Moreover, some populations have remained susceptible to infection, due to vaccine hesitancy or being immune-compromised, and in the developing world less than 15% of the population got vaccinated.

There is an urgent need to establish collections of broad spectrum anti-viral drugs that can be rapidly deployed against emergent viral infections.

We have demonstrated that a recombinant form of the α-dystroglycan N-terminal domain  (α-DGN) we over-produce in bacteria is highly effective against a wide spectrum of enveloped viruses from different virus families and potentially their variants (coronaviruses, Influenza, Dengue, RSV, TBEV), both in vitro in human cell lines and human gut organoids and in vivo in a humanized mouse model. Our overarching aim is to employ our recombinantly produced α-DGN (Dystrovir) as a tool for reducing the spread of viruses at the early stages of transmission in an out-patient or community setting. This approach differs from repurposed drugs as Dystrovir would be both potent and non-toxic and available for immediate use as 'gold standard' for viral infections and early containment of epidemics.

α-Dystroglycan N-term (α-DGN)

α-Dystroglycan (α-DG) is a basement membrane receptor that links the extracellular matrix to the cytoskeleton. α-DG gets proteolytically cleaved and its N-terminal domain (α-DGN), found in small amounts into sera, has been shown to have a protective role against Influenza A virus infection in mice. Based on our expertise on this system, we recombinantly overexpressed and purified a stabilised version of α-DGN (Dystrovir, MW 30kDa), , both from human and mouse (the two proteins share 93% sequence identity), and further shortened it to mS6 (15kDa), comprising its S6 domain only (Fig. 1). Both protein fragments exhibit a broad and potent antiviral activity against infection of a number of enveloped viruses including SARS-CoV-2, SARS-CoV, MERS CoV, IAV, RSV, TBEV and the 4 serotypes of DENV.

Related Sustainable Development Goals: 

Sustainable Development Goal 3 Good Health and Wellbeing represented by a heart activity line an image of a

Cite the research

Maria Giulia Bigotti, et al. The α-dystroglycan N-terminus is a broad-spectrum antiviral agent against SARS-CoV-2 and enveloped viruses. Antiviral Research, Volume 224, April 2024, 105837. https://www.sciencedirect.com/science/article/pii/S0166354224000457?via%3Dihub 

Connect with the researchers

Guilia Bigotti, Research Fellow, Bristol Medical School

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