Finding new approaches for therapeutics against Ebola virus
Press release issued: 4 September 2014
Researchers from the Universities of Liverpool and Bristol, in collaboration with Public Health England, have been investigating new ways to identify drugs that could be used to treat Ebola virus infection.
Their approach has been to study what proteins inside a cell are critical for the functions of Ebola virus and are hijacked by the virus to help with infection. One of the proteins they have targeted is known as VP24. This protein disrupts signalling in infected human cells and disrupts the body’s immune system and the fight against the virus.
Once the team identified these cellular proteins they were able to find out whether any drugs were already in existence that could block the function of the particular protein. One such drug identified was ouabain, which can be used in the treatment of heart of disease. Administering this drug reduced virus replication in treated cells.
The study was led by Professor Julian Hiscox from the University of Liverpool’s Institute of Infection and Global Health and Professor Roger Hewson at Public Health England.
Professor Hiscox said: “This study shows how existing therapeutics can be identified and potentially repurposed for anti-viral therapy, and the technique of using existing and tested drugs for a different purpose can save considerable time and, ultimately lives.”
Disrupting cellular proteins important for viruses also has the potential to tackle the problem of resistance to medication. Since the cellular proteins are effectively evolutionarily static, the virus won’t be able to adapt to defeat it – as is increasingly the case with treatment by anti-virals used against viral proteins such as seen with influenza virus and HIV infection.
The study, which also involved Dr David Matthews from the University of Bristol, was a collaboration with Public Health England and used the unique specialist facilities at PHE Porton, which are designed to safely work with viruses such as Ebola under conditions of high containment.
Dr Matthews, from the School of Cellular and Molecular Medicine, said: “We are very excited about the longer term potential of this kind of work, it shows how we can use what is called a ‘systems virology’ approach to help us understand how a virus interacts with and subverts our own biological processes for its own ends.
“We can then look for drugs licensed to treat an unrelated human condition that affect the same biological processes and, in theory, use this drug to slow the virus down. Clearly a lot more work needs to be done before it could be used but this is a great first step.”
Co-author Professor Miles Carroll, Head of Research at PHE Porton, said: “This research highlights the anti-viral effects of an already available and licensed human drug which might prove beneficial in a therapeutic setting.”
Professor Hiscox concluded: “The philosophy of transiently targeting the function of host cell proteins that are critical for virus infection holds great promise not only for increasing the potential arsenal of drugs against Ebola but other viruses as well.”
The paper ‘Elucidation of the Ebola virus VP24 cellular interactome and disruption of virus biology through targeted inhibition of host cell protein function’, was a collaboration between the University of Liverpool, Public Health England, the University of Bristol and the Health Protection Research Unit in Emerging and Zoonotic Infections. It is published in the Journal of Proteome Research.