Researchers at the Walter and Eliza Hall Institute of Medical Research have shown that a new drug compound can prevent long COVID symptoms in mice.
The world-first study found mice treated with the antiviral compound, developed by a multidisciplinary research team at WEHI, were protected from long-term brain and lung dysfunction. These are key symptoms of long COVID.
The researchers hope the results could lead to in-human clinical trials and a potential treatment.
Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a chronic condition characterised by symptoms that last for weeks or months after contracting the virus.
It is a significant health burden that remains poorly understood, with symptoms ranging from breathing difficulties to brain fog and chronic fatigue.
Despite millions of people worldwide reporting these symptoms, the cause of long COVID remains largely unknown, and there is no approved treatment for the disease.
Corresponding author and WEHI Laboratory Head, Dr Marcel Doerflinger, said the results could be a turning point in the hunt for treatments to support people at risk of developing this condition.
“With 5 per cent of people who contract COVID-19 going on to develop long COVID, the disease has morphed into a silent pandemic where millions are battling symptoms with more questions than answers,” said Dr Doerflinger.
“Our pre-clinical studies have achieved something no currently approved therapy has done to date - preventing the most debilitating symptoms of long COVID in mice.
“While more research is needed to develop a drug that can be used in humans, seeing these milestone results in the unique mouse models developed at WEHI suggests this could be a real possibility in the future, which is incredibly exciting."
Currently approved therapies for COVID-19 target a critical coronavirus protein known as Mpro. In 2020, WEHI researchers identified another protein, PLpro, as a promising drug target.
Professor David Komander has spent over 15 years studying the family of proteins, including PLpro, and co-led the large, multidisciplinary WEHI team that spearheaded the discovery of new PLpro inhibitors.
The team turned to the National Drug Discovery Centre (NDDC) at WEHI) to find a new drug compound targeting this critical protein.
“Existing drugs had hit several hurdles to be effective in blocking PLpro in cells – our team wanted to see if we could find new ones capable of overcoming these barriers,” said Professor Komander, a corresponding author and Division Head at WEHI.
“In order to do this, we screened over 400,000 compounds to see if we could uncover novel drug-like molecules that had potential against this protein.
“To have identified a drug target and then develop a novel drug compound against it in less than five years is an incredible feat that would have been impossible without the advanced technologies, speed and scale of the NDDC and multidisciplinary team at WEHI.”
Dr Shane Devine, a co-first and corresponding author on the paper, said the team also found their novel compound can potentially treat acute COVID better than currently available antivirals for the disease.
“Our study has provided the first evidence to prove PLpro is a powerful new drug target for COVID-19 treatments while also showing its potential ability to treat the virus with unprecedented efficacy,” said Dr Devine.
The project will continue collaborating with the Centre for Drug Candidate Optimisation and the Monash Institute of Pharmaceutical Sciences to evaluate the biopharmaceutical properties of this antiviral compound.
The research is supported by the Medical Research Future Fund, the Wellcome Trust and philanthropic donations for COVID research and translation.