More than $1.3 million awarded for new COVID-19 research at Monash

Five Monash University projects investigating treatments for COVID-19, including a potential inhaled treatment, have been awarded funding by the Medical Research Future Fund (MRFF).

Federal Health Minister, The Honourable Greg Hunt, announced more than $1.3 million for four Monash research projects as part of a $66 million fund to contribute to global efforts to control and eliminate the virus. The MRFF’s Coronavirus Research Response is part of the Australian Government’s $8 billion Coronavirus (COVID-19) National Health Plan.

Projects funded include:

Investigating inhaled treatments for COVID-19: Professor Merlin Thomas

A collaborative research project between Monash and Murdoch University is investigating a potential inhaled treatment for COVID-19 that has a different mechanism than other treatments and vaccines in development.

COVID-19 is caused by a coronavirus that uses the cell-surface protein, Angiotensin-Converting Enzyme 2 (ACE2), to access and infect cells of the lung. Most vaccines and other potential treatments focus on blocking the coronavirus.

Professor Thomas and team have taken a different approach, by targeting ACE2. They have discovered a novel way to change ACE2 in order to prevent the coronavirus using it to get into cells. Moreover, they can now do this without losing the good things that ACE2 does in the lung.

“With this support from the MRFF, over the next few months, we will further optimise this inhaled treatment. We believe that in early-stage COVID-19, transient, selective and safe modulation of ACE2 using an inhaler will reduce the coronavirus burden and keep people from getting sick enough to end up in hospital, on a ventilator or die. Thanks to the MRFF for their support and the hard work of the research team at Monash Central Clinical School and Murdoch University (WA) at this challenging time,” said Professor Thomas.

Investigating antiviral drug Ivermectin for COVID-19: Dr Kylie Wagstaff

Dr Kylie Wagstaff and team have identified Ivermectin, an FDA-approved marketed anti-parasitic drug, as a potential antiviral for the COVID-19 causative virus, SARS-CoV-2.

Preliminary work demonstrates that Ivermectin significantly reduces viral replication (~5000 fold by 48h) in vitro and therefore has the potential to reduce viral load. This is an established antiviral treatment strategy, which could meet a huge unmet need in COVID-19 treatment and prevention.

This project will address some remaining pre-clinical questions around Ivermectin as well as to confirm the mechanism of action (host-targeted versus virus-targeted) and examine other compounds in the same class with similar mechanisms of action. The team will also examine whether Ivermectin can work in combination with other potential anti-COVID-19 compounds.

These studies will inform stage 2 clinical studies, which, given the extensive use of Ivermectin in people over the last 30 years and the extensive safety and pharmacokinetic data already existing, can be potentially expedited.

“Ivermectin is a safe, low-cost, widely available drug (it is on the WHO model list of essential medicines) and is worthy of further investigation against SARS-CoV-2,” Dr Wagstaff said.

Convalescent plasma for COVID-19: Associate Professor Zoe McQuilten

This study will evaluate whether plasma collected from people who have recovered from COVID-19 containing antibodies against the virus can act as a treatment for patients admitted to hospital or intensive care with COVID-19.

In partnership with Australian Red Cross Lifeblood, the team will establish the process to collect, test and administer the convalescent plasma. The researchers will test whether it is safe and effective in two large, multicentre, national clinical trials.

“The research is important because if we demonstrate safety and efficacy, then this product could be rapidly made widely available for treatment of patients with COVID-19,” said Associate Professor McQuilten.

Novel inhibitors of SARS coronaviruses targeting ACE2: Professor Robert Widdop

Antiviral agents for COVID-19 are urgently needed to treat patients to reduce morbidity and mortality. The surface of the virus is decorated in trimeric spike proteins that attach the virus to the cell membrane by binding to the protein known as angiotensin-converting enzyme 2 (ACE2).

A team from the Monash Biomedicine Discovery Institute, including Professor Widdop, Dr Mark Del Borgo, Professor Mibel Aguilar and Associate Professor Fasseli Coulibaly, have developed peptides closely related to the substrate of ACE2 that inhibits the catalytic activity of ACE2. These will be evaluated for their potential antiviral activity and to define their mechanism of action, in collaboration with the Burnet Institute, as part of a MRFF-funded project. If successful, the team will move into a second stage with Monash Health/Alfred Hospital networks and MIPS, and has wide networks for overseas deployment into clinical studies.

“Ideally, this will allow us to create an antiviral treatment that can be used on ill COVID-19 patients that potentially could be ready before a vaccine, if we have peptides with sufficient antiviral efficacy,” said Professor Widdop.

Stem-cell derived human tissue models for the identification of drugs to treat COVID-19: Professor José Polo

This project will use in vitro organ models derived from human stem cells to establish more sophisticated SARS-CoV-2 infection models, and use those models to identify drugs with antiviral activity against SARS-CoV-2. This is a collaborative research project between the Doherty Institute, Monash University and the Murdoch Children’s Research Institute.

Professor Polo’s team have used their capabilities to generate human lung cells from iPSCs to develop an in vitro model that more accurately reflects the infected lungs of a patient. This in vitro lung model expresses the two receptors that the virus requires for infection and the team - together with Professor Kanta Subbarao’s group at the Doherty Institute - have demonstrated that the cells are infected by SARS-CoV-2. The goal now is to optimise this in vitro model of human lung infection so that it can be deployed as an enhanced drug screening platform.

"We are very excited that we could rapidly deploy our existing knowledge in stem cell differentiation and were able to develop an in vitro model of the lung that will allow us to model SARS-CoV-2 infection in humans and thus improve our chances to find a cure for COVID19,” Professor Polo said.

To view all approved projects, please visit: greghunt.com.au/66-million-for-coronavirus-related-research/