Professor Luke O’Neill wants to stop both the virus and the massive immune response, and he is exploring how a naturally-occurring substance in the body could do that.
The substance is called itaconate, and it is a byproduct of a well-known biochemical pathway in cells called the Krebs cycle. “Our lab has been looking at how cells of the immune system burn nutrients, and we found that when the immune system is reacting to something, when it is going into a state of inflammation, you get these byproducts,” explains Professor O’Neill, who is Professor of Biochemistry at Trinity College Dublin and whose research has been supported by SFI.
“One of the byproducts is itaconate, and we think it acts as a brake on inflammation, which could be useful for stopping a massive immune response that could be damaging.”
In lab tests, itaconate has been able to stop inflammation in models of sepsis and lupus (both are conditions where an over-active immune response causes damage), but interestingly the substance has also been shown to act against viruses such as Zika virus and Influenza in the lab.
“We have been looking at this for a while, and a company I co-founded, Sitryx, is interested in our work,” says Professor O’Neill. “Now, through a collaboration with scientists in Holland on the EU-funded INITIATE project, we are testing to see how the substance works against the virus that causes COVID-19.”
Many anti-inflammatory drugs are being tested for the new virus, and Professor O’Neill hopes that itaconate will be another ‘shot on goal’. “We need to throw everything we can at this virus, and see what works well, might work in subgroups of patients and what has the least side effects,” he says. “We are fortunate that because of our past basic research, which SFI supported over a number of years, we are in a position to be able to test this potential anti-inflammatory and anti-viral agent now for the pandemic.”