The funding from the Medical Research Future Fund (MRFF) will support two Institute research programs, part of a $66M investment by the Australian Government in research efforts to combat COVID-19. The grants were announced today by Australian Health Minister the Hon. Greg Hunt MP at the Walter and Eliza Hall Institute.
The two Institute programs are developing new medicines for COVID-19 and other coronaviruses, by leveraging the Institute’s established expertise in infectious disease research, protein biology, drug discovery, high-throughput screening and medicinal chemistry.
The new funding from the MRFF is an important boost to the Walter and Eliza Hall Institute’s research efforts to tackle COVID-19. This includes programs that are developing better ways to diagnose COVID-19, as well as new preventative and treatment strategies.
COVID-19 is caused by the SARS-CoV-2 coronavirus – part of a family of viruses that include the causative agents of SARS and MERS. The Institute’s COVID-19 research is being undertaken both with the aim of combatting the current COVID-19 pandemic, as well as contributing to a new ‘tool kit’ of strategies that could be rapidly deployed to combat any future coronavirus outbreaks.
The MRFF grants will provide vital funding for two Institute research programs that are taking different approaches to develop new medicines for COVID-19.
One program, VirDUB, is focussed on discovering drugs that block a coronavirus protein called PLpro. This protein, found in all coronaviruses, is essential for the virus to hijack human cells and disable their anti-viral defences.
Professor David Komander, who is leading VirDUB, said PLpro mediates a process called ‘deubiquitination’, that alters proteins in cells. “PLPro is very similar to human and viral ‘deubiquitinase’ (DUB) proteins that my team has studied for many years. We know DUBs are ideal targets for drug discovery. Here, we want to directly stop an essential viral DUB from functioning within cells to break the viral life cycle,” he said.
The new MRFF funding will accelerate VirDUB’s work towards new drugs that inhibit coronavirus PLpro. The program brings together researchers at the Institute with expertise in deubiquitination, structural biology, medicinal chemistry, drug discovery and virology, and accesses the infrastructure of the National Drug Discovery Centre, a facility based at the Walter and Eliza Hall Institute.
“Drugs that inhibit PLpro could potentially be used to treat people in early stages of COVID-19, as well as to protect people from infection. By targeting a viral system that is found in a range of coronaviruses, VirDUB may lead to new medicines that could be available to tackle potential future disease outbreaks caused by other coronaviruses,” Professor Komander said.
The second program, led by Associate Professor Wai-Hong Tham, is developing new ‘biologics’ medicines to prevent or treat COVID-19. Biologics are medicines that mimic naturally occurring proteins such as antibodies – immune proteins that fight infection. Antibodies are already in clinical use for diseases such as cancer and inflammatory and autoimmune conditions. Associate Professor Tham said her program is searching for new biologics medicines that prevent the COVID-19 coronavirus, SARS-CoV-2, from binding to human lung cells – the first step in the virus infection cycle.
“Our consortium is searching for antibodies that block the interaction between the ‘spike’ protein on the surface of the SARS-CoV-2 virus and the ACE2 receptor on human lung cells. These two proteins form the ‘lock and key’ system through which SARS-CoV-2 invades cells. If we can block these proteins’ interactions, we stop the virus infecting a cell,” she said. “Biologics medicines for COVID-19 could be important tools for preventing infections as well as treating people in the early stages of the disease.”
The biologics research program brings together the expertise of Victorian and Australian academic and industry leaders in infectious diseases and antibody therapeutics, at the Walter and Eliza Hall Institute, the Peter Doherty Institute, CSL, Affinity Bio, CSIRO, Burnet Institute and Kirby Institute. The research has also been boosted by a $500,000 funding grant from the Victorian Government.
Walter and Eliza Hall Institute director Professor Doug Hilton AO said the Institute had responded rapidly to the COVID-19 pandemic, by applying a diverse range of research expertise built over many years.
“We are thrilled to receive funding from the MRFF for these two key programs within our COVID-19 research portfolio, in addition to the support already provided by MRFF for the COVID SHIELD clinical trial,” he said.
“The two newly funded Institute programs are extremely promising, and could provide important steps to better control COVID-19, as well as providing vital new weapons that could be deployed against potential future coronavirus disease outbreaks,” he said.
Professor Hilton said the MRFF is a valuable and innovative approach to funding medical research.
“I am thrilled to see how the MRFF has been used by the Australian Government to rapidly support urgently needed COVID-19 research. Traditional funding cycles in Australia take many months from application to the delivery of funds, and in the current pandemic, that is time we don’t have. We need relevant research given every chance to succeed, as rapidly as possible.
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