Ten teams from institutions across Australia and the UK received a collective AU$5 million in Round Two of the Foundation Grants for projects to develop novel therapeutics for pathogens of pandemic potential, in line with the Centre’s mission.
Lead investigators and co-investigators
Dr Naphak Modhiran, The University of Queensland
Broad-spectrum antibody therapy for Japanese Encephalitis serocomplex viruses
$599,467.00
Co-investigators: Dr Martina Jones, Prof David Asher, A/Prof Daniel Watterson, Dr Yu Shang Low, Dr Alberto Amarilla and Dr Connor Scott.
Japanese Encephalitis serocomplex viruses (JESV), including West Nile, JE, St. Louis encephalitis virus, represent an ongoing threat to human health, with the potential for new virus emergence. There are no approved therapies for any viruses in this group. Our project aims to isolate broad-spectrum human antibodies as new therapies for this group of important human pathogens. This is enabled by our innovative antigen-presenting platform and computational approaches to predict outbreak variants and specifically target conserved epitopes on virus surfaces. Outcomes from this research allows the discovery and preclinical development of the first pan-JESV antibodies, adaptable for use in outbreak scenarios.
Prof Wai-Hong Tham, The Walter and Eliza Institute of Medical Research
Rapid and adaptable nanobody platform for generation of therapeutics against pathogens of pandemic potential
$598,312.48
Co-investigators: Prof Colin Pouton, A/Prof Melissa Call and Dr Phillip Pymm.
Monoclonal antibodies have revolutionised modern medicine with treatment of previously untreatable cancers and inflammatory diseases, representing seven of the top ten best selling drugs in 2021. Nanobodies are single domain antibodies derived from camelids and represent the smallest naturally occurring antigen-binding domain. Due to their small size, increased stability and cheaper manufacturing compared to conventional antibodies, they are an increasingly important class of monoclonal antibodies for therapeutics. Here we develop a rapid and adaptable nanobody platform using mRNA immunisation, single B cell cloning, deep mutational scanning, and high throughput characterization to identify nanobodies against pathogens of pandemic potential.
Dr Larissa Dirr, Griffith University
Development of a broad-spectrum neuraminidase inhibitor for respiratory viral infections
$557,097.00
Co-investigators: Prof Armin Braun, Dr Ibrahim El-Deeb, Dr Patrice Guillon and Prof Mark Von Itzstein.
Flu, croup/bronchiolitis and mumps are viral diseases associated with serious health, medical and economic burdens. We identified a multi-pathogen drug candidate that has the potential to prevent and treat these viral infections. Optimising this molecule will improve and significantly accelerate treatment delivery to patients, ultimately reducing mortality and morbidity associated with these diseases.
Prof Gavin Wright, University of York
Identifying human cell surface receptors for viruses of pandemic potential using a new platform technology to develop decoy receptor therapeutics and quantify zoonotic risk
$599,998.75
Co-investigators: Dr Dalan Bailey
To infect our cells, viruses must specifically bind to surface receptor molecules. Discovering which human receptors are used by viruses is crucial for developing new broadly-acting antiviral therapeutics based on soluble “decoy” receptors that block infection. We are proposing to exploit a new and unique receptor screening platform to discover which human receptor/s are used by up to 200 different animal viruses. The results of this research could lead to a set of pandemic ready decoy receptor anti-viral therapeutics and also identify which animal viruses are poised to infect humans and therefore of increased risk of causing pandemics.
Dr Annette von Delft, University of Oxford
Discovery of novel, broad-spectrum peptides targeting pandemic and seasonal influenza neuraminidases
$300,000.00
Co-investigators: Dr Pramila Rijal, Dr Jon Elkins, Prof Paul Brennan and Prof Alain Townsend.
To prepare for future pandemics, novel therapies are of utmost importance. We propose to combine cutting-edge drug discovery peptide technology with novel data on the influenza protein neuraminidase. The neuraminidase is essential for the viral life cycle; inhibiting it effectively treats infection in patients. However, the virus accumulates resistance mutations upon exposure to existing treatments, rendering them ineffective. We envisage our novel inhibitors to be effective against multiple influenza strains, with a high barrier to resistance due to size and constrained composition. Further, we will provide proof-of-concept that the technology platform can be deployed in case of future pandemics.
Dr Aaron Brice, CSIRO
Aptamer therapeutics for highly pathogenic pandemic viruses
$300,000.00
Co-investigators: Dr Cameron Stewart and Dr Marina Alexander.
Several virus families of pandemic concern lack therapeutics that are essential for rapidly responding to pandemic emergence. Drug development for highly pathogenic viruses, such as Hendra and Ebola viruses, is hampered by restriction to high-containment laboratories. Utilising our capability for high-content screening involving highly pathogenic viruses, this project will identify novel antiviral ‘aptamers’ targeting these viruses. This novel class of therapeutic allow for rapid candidate identification, and are cheaper and quicker to produce, compared to typical drugs, while being highly specific for their target. The outcomes of this project will mitigate the health, social and economic impacts of future pandemics.
Prof Michelle McIntosh, Monash University
Developing an inhaled delivery platform for antiviral therapeutics
$599,071.00
Co-investigators: Dr Jie Tang and Prof Colin Pouton.
RNA viruses pose a global health threat, demanding innovative solutions. This project aims to develop inhalable therapy for viruses, merging cutting-edge research in gene editing and nanomaterials with a formulation designed to achieve maximal airway coverage. This will enable swift reactions to future pandemics, effective and direct virus eradication in the lungs, and convenient inhaler use to avoid the need for injections which would accelerate the rollout of a new therapeutic. This innovation promises a game-changing solution, ensuring both efficacy and broad acceptance in the global battle against respiratory viruses.
Prof David Komander, The Walter and Eliza Institute of Medical Research
Antivirals targeting papain-like protease (PLpro)
$598,332.00
Co-investigators: Dr Shane Devine, Mr Dale Calleja, Prof Guillaume Lessene and A/Prof Kym Lowes.
Novel human coronaviruses will continue to emerge and future-proofing against this scenario is crucial to ensuring public health. We aim to conquer future coronavirus driven pandemics by generating antivirals with broad-spectrum activity. These antivirals will significantly ease the health burden in support of future vaccination efforts. Our program targets an essential protein, PLpro, present in all coronaviruses for which no drugs are currently available. In a world-first, we have developed small molecules that target PLpro across diverse coronavirus species. Excitingly, these potent compounds display excellent drug-like properties and prospects as the next antiviral drug in future pandemics.
Dr Glenn Marsh, CSIRO
Establishing an International Centre for Henipaviruses and discovery of pan-henipavirus therapeutics.
$500,000.00
Co-investigators: Prof Johan Neyts.
Henipaviruses, including bat-borne Hendra and Nipah viruses, can infect a wide-range of mammals and in humans cause severe often-fatal disease. Due to this henipaviruses are classified as risk group 4 pathogens. Over recent years the discovery of many new henipaviruses, including rodent- and shrew-borne henipaviruses, has further raised concerns about the pandemic potential of this virus group. This project will establish capabilities to test Henipaviruses for susceptibility to previously identified candidate antivirals, with an aim of identifying antivirals that are broadly effective across this virus genus. In addition, host targets for antiviral discovery will be identified for targeted drug development.
Prof Anthony Kelleher, University of New South Wales
Self-amplifying mRNA Antiviral RNA Therapeutics (SMART) platform
$300,000.00
Co-investigators: Prof Robin Shattock, Dr Chantelle Ahlenstiel, Dr Scott Ledger, Prof Maria Kavallaris, Dr Roger Liang, Prof Daniela Traini, Prof Nathan Bartlett, Prof Cees Van Rijn, Prof Philip Hansbro and Prof Pall Thordarson.
Novel antiviral therapeutic platform technology is urgently needed for pathogens of pandemic potential. We have developed antiviral short-interfering (si)RNA therapeutics targeting the COVID-causing virus to shut-down infection against all SARS-CoV-2 variants, however their effect is transient. We propose to develop the highly innovative SMART (Self-amplifying mRNA Antiviral RNA Therapeutics) platform targeting the SARS-coronavirus family to increase the duration of antiviral siRNA effectiveness. We will package the self-amplifying (sa)RNA similar to COVID mRNA vaccines and confirm effectiveness in a mouse infection model. The SMART platform will provide broad-spectrum antiviral therapeutics for SARS-coronaviruses and provide preparedness for pathogens of pandemic potential.