An international collaboration, including scientists from Trinity College Dublin has potentially unlocked the door to better treatment of viral diseases, including the flu and the common cold. The results from their study which investigated how viruses cause disease in humans were published in the prestigious scientific and medical journal Nature Communications.
The researchers discovered that an ancient, 1.5 billion year old cell biological process found in plants, fungi and mammals enhances viral disease in mice and the researchers believe it is highly likely it has the same effect on viruses in humans.
They identified a protein, called Nox2 oxidase that was activated following infection with viruses, including influenza, rhinovirus (i.e. common cold), dengue and HIV, irrespective of the strain of the virus. Once activated the Nox2 oxidase suppressed the body’s key antiviral reaction and its ability to fight and clear the viral infection which in turn resulted in a stronger or more virulent disease in mice.
The study also investigated a new prototype drug to treat these debilitating viral diseases. They found that the Nox2 oxidase protein activated by the viruses is located in a cell compartment called endosomes. They carefully modified a chemical that inhibited or restrained the activity of the Nox2 oxidase, to enable it to reach this endosome compartment. Their customised drug was found to be very effective at suppressing disease caused by influenza infection.
In the 2015/16 flu season in Ireland 1856 people were hospitalised as a result of flu, there were 84 deaths from flu and at peak flu season, 80 in every 100,000 of the population had the flu, according to the HSE influenza surveillance reports. The global burden is also staggering with more than 5 million cases of infection annually with up to 10% resulting in death.
The collaboration was led by RMIT University scientists in Melbourne and includes researchers and clinicians from eight universities across Australia, the United States and Trinity College Dublin in Ireland.
Professor John O’Leary, Chair of Pathology at Trinity, Consultant Pathologist, St. James's Hospital and The Coombe Women and Infants University Hospital Dublin and contributing author on the study said: “The findings of this international study are hugely important in terms of the fight against viral epidemics and pandemics. Standard anti-viral therapies in general target the virus directly. This new research highlights how viruses disrupt normal cells and a key molecule that regulates this disruption. By selective targeting of this molecule, a new era in viral infected cell treatment will be ushered in.”
Dr Selemidis, head of the Oxidant and Inflammation Biology Group at RMIT University said: “Current treatment strategies are limited as they specifically target circulating viruses and have either unknown or very little effect against new viruses that enter the human population."
“The study identifies a protein of the immune system that contributes to the disease caused by flu viruses irrespective of their strain. It also developed a novel drug delivery system to target this protein, which drastically alleviated the burden of viral disease."
”This work identifies a treatment strategy that has the potential to alleviate the symptoms caused by some of the most devastating viruses worldwide, including the flu,” Dr Eunice To said.
Dr Selemidis’ laboratory at the School of Health and Biomedical Sciences at RMIT University, Trinity College Dublin and the other collaborators are pursuing further research to aid the development of novel drugs for preclinical and clinical trials.
This research was funded nationally by the National Health and Medical Research Council of Australia and the Australian Research Council.