Collaborative research between Murdoch University and Monash University is bringing the world one step closer to an effective treatment for COVID-19.
The COVID-19 pandemic has taken the world by storm this year, with researchers working towards a vaccine globally.
Researchers from Murdoch and Monash University are taking a unique approach by developing a short-term inhaled treatment for the virus that alters our own cells.
“Everyone is trying to come up with a vaccine that targets the virus. What our approach does is target people,” said Professor Steve Wilton, who leads the Centre for Molecular Medicine and Innovative Therapeutics at Murdoch.
We are trying to alter the host cells to make the person more resistant to viral infection, and we aren’t aware of anyone else doing it.”
Supported by the award of a nine-month grant from the Medical Research Future Fund, this joint venture is led by Professor Merlin Thomas at Monash University, with Professor Wilton leading the research in Perth, along with Dr May Aung-Htut.
Professor Wilton is Director of both the Perron Institute for Neurological and Translational Science as well as the Centre for Molecular Medicine and Innovative Therapeutics.
How the treatment works
COVID-19 is caused by a coronavirus that uses a cell-surface protein, called Angiotensin-Converting Enzyme 2 (ACE2), to access and infect cells in the lungs.
While most vaccines and other potential treatments focus on blocking the coronavirus, Professor Thomas and Professor Wilton are targeting ACE2 by changing the protein in a way that prevents COVID-19 from latching onto our cells.
“What we are doing is making the ACE2 surface protein soluble, so instead of COVID-19 being able to latch onto the cell, it floats around. As it can’t attach to the cell, the viral infection should slow down,” Professor Wilton explained.
“It is not the first coronavirus that uses ACE2 for host cell entry and it probably will not be the last” Professor Thomas said.
“This makes selective and transient modulation of lung ACE2 an attractive and high priority antiviral target as viruses change, but ACE2 will not.”
This novel approach slows down the rate of infection in two ways: whilst protecting the cells from viral attachment and infection while the new modified ACE2 becomes a soluble decoy to the virus.
“The danger of COVID-19 is that it can cause an intense immune response in the lungs, however if you can slow the infection rate, that gives you a greater chance to mount an effective immune response. Then you won’t need a vaccine.”
Building on rare disease treatments
“We have considerable experience in designing this type of treatment for the past two decades in the realm of rare diseases. We can modify and optimise it so it’s very efficient at a low dosage,” said Professor Wilton.
The new COVID treatment uses the same technology that Professor Wilton and Professor Sue Fletcher used to develop treatments for Duchenne Muscular Dystrophy (DMD).
The DMD treatments developed by the Perth team exploit cell gene expression machinery to trick cells into ‘skipping’ over the disease-causing error, acting as genetic ‘whiteout’.
Boys receiving the exon skipping treatment in the United States have maintained the ability to walk into their mid- to late-teens, whereas without treatment, they would expect to be wheelchair bound around 12 years of age.
“The concept of tricking cells to skip genetic errors to treat Duchenne Muscular Dystrophy evolved during my development of diagnostic screening for neuromuscular diseases,” Professor Wilton said.
“We hadn’t considered extending our research into infectious diseases, such as COVID-19, until approached by Professor Thomas at Monash University.
"We had already been collaborating on other projects for several years and the exciting aspect about the ACE2 research is that we can widen the scope of our antisense rare disease research for everyone at risk of coronavirus infections.”