Cancer drug dampens COVID-related inflammation

Dr Dominic De Nardo is a Group Leader in the Department of Biochemistry & Molecular Biology, Immunity Program within the Monash Biomedicine Discovery Institute.
Dr Dominic De Nardo is a Group Leader in the Department of Biochemistry & Molecular Biology, Immunity Program within the Monash Biomedicine Discovery Institute.

A cancer drug could play an important role in limiting the damaging effects of lung disease in COVID-19 patients, thanks to new research co-led by Hudson Institute of Medical Research, Monash University's Biomedicine Discovery Institute (BDI) and the Centenary Institute.

The body’s inflammatory response to infection is important in controlling viruses, such as SARS-CoV-2, the virus that causes COVID-19, but when inflammation gets out of control the effects can be lethal.

Now a team co-led by Associate Professor Michael Gantier (Hudson Institute of Medical Research), Dr Dominic De Nardo (Monash BDI) and Professor Phil Hansbro (Centenary Institute) has found that idronoxil, which was originally designed to treat cancers, can reduce the inflammation that occurs in a pre-clinical model of COVID-19.

Their research was published yesterday in Nature Communications.

Immune system overdrive

Dr Dominic De Nardo is a senior co-author on the paper. He said that there were three main aspects of this collaborative research project.

“Michael Gantier’s team showed that idronoxyl had anti-inflammatory potential. Our team at Monash BDI provided insights into the mechanism of its action, demonstrating how the drug was impacting the innate immune system. And the Centenary Institute team led by Phil Hansbro used a pre-clinical model of COVID-19, which showed that the drug could significantly reduce associated inflammation,” said Dr De Nardo.

“Early in the COVID-19 pandemic we realised that uncontrolled inflammation was one of the major life-threatening aspects of the infection, but we didn’t know exactly how this inflammation occurred,” Associate Professor Gantier said.

“While fighting the infection caused by SARS-CoV-2, our immune system can sometimes go in overdrive - i.e. when the off-switch does not work.

“The problem is that blocking the immune response too early can help the virus better replicate and do more damage.

“We’ve now shown that therapeutic targeting of a single protein activated by several inflammatory pathways can help limit the bad inflammation, without increasing viral replication in the lung,” he said.

“This led us to discover that a drug called idronoxil administered 3 days after infection could reduce the inflammation resulting from SARS-CoV-2 infection in a pre-clinical model of the severe disease.”

“In other words, we can let the body’s inflammatory response go to work without going too far – we’ve restored the off-switch.”

This preclinical work was conducted in parallel with an early clinical trial on moderate SARS-CoV-2 patients in 2021, which demonstrated that idronoxil was safe in this disease context.

Collaborators on this project also include UTS and Centenary Institute, Australian National University, St. Vincent’s Institute of Medical Research, UNSW, University of Adelaide, Francis Crick Institute and Noxopharm Limited.

Read the Nature Communications paper, Pharmacological inhibition of TBK1/IKKε blunts immunopathology in a murine model of SARS-CoV-2 infection

DOI: 10.1038/s41467-023-41381-9

About Monash Biomedicine Discovery Institute

Committed to making the discoveries that will relieve the future burden of disease, the Monash Biomedicine Discovery Institute (BDI) at Monash University brings together more than 120 internationally-renowned research teams. Spanning seven discovery programs across Cancer, Cardiovascular Disease, Development and Stem Cells, Infection, Immunity, Metabolism, Diabetes and Obesity, and Neuroscience, Monash BDI is one of the largest biomedical research institutes in Australia. Our researchers are supported by world-class technology and infrastructure, and partner with industry, clinicians and researchers internationally to enhance lives through discovery.