Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymera ....Novel target of amiloride analogues - picornaviral RNA polymerase. Picornaviruses cause a range of diseases such as poliomyelitis, meningitis, myocarditis, hepatitis A, neonatal sepsis and common cold. No antiviral treatment is available for these infections. Nearly 50% of antiviral drugs used in medicine are viral polymerase inhibitors; however picornaviral RNA polymerase has been largely overlooked as a drug target. We have discovered a group of compounds that inhibit picornaviral RNA polymerase. This project aims to define the inhibition mechanism and to evaluate a potential use of these compounds for antiviral drug development.Read moreRead less
Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may ....Structure-based discovery of anti-rotaviral agents. Rotavirus causes, particularly in children under 5 years of age, significant loss of life worldwide. Over 600,000 children under 5 years of age per annum die as a result of rotavirus infection. Australia records over 10,000 hospitalisations per annum due to rotavirus infection. This project aims, using structure-based drug design techniques, to develop inhibitors of a rotavirus protein that is essential in its lifecycle. These inhibitors may lead to the development of useful drugs to treat rotavirus infection and may reduce significant loss of life caused by this deadly virus.Read moreRead less
Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to prod ....Structure-based discovery of anti-parainfluenza viral agents. Respiratory diseases, for example croup and bronchitis, in children are caused in the main by human parainfluenza viruses (hPIVs) types 1-3. No vaccines or specific antiviral therapy against hPIV infections exist. This project targets an essential protein in the virus' lifecycle. The essential triple role of the protein in virus spread makes it an attractive target for the development of hPIV-specific drugs. This project aims to produce lead-like compounds that inhibit the protein's function and may provide novel drug candidates for further development. Furthermore the role of human host cell-associated carbohydrates in parainfluenza infection will be better understood.Read moreRead less
The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in ....The dynamics of viral latency in chronic infection. Although many acute infections can now be controlled, we still suffer from a large number of chronic infections such as HIV or herpes that cannot be eradicated. Many of these infections persist because they can lie dormant in a 'latent' state. How this latent state is established, and how long it lasts are important to understand if we want to control these infections. We have assembled a team of mathematicians, immunologists and virologists in order to study latent infection at the cellular level, and within infected monkeys. This will provide the first insights into the dynamics of latency - how these cells are produced and die - and should lead to novel approaches to controlling chronic infection.Read moreRead less
Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produce ....Design and Development of HIV-1 Integrase Inhibitors Based on a Natural Product Lead. HIV/AIDS is a significant health problem with over 40 million people infected with HIV worldwide. Resistance to current drugs is rising rapidly and new therapeutics are urgently needed. This project will bring together local expertise in organic synthesis and virology in order to develop new and better treatments for HIV/AIDS. Ultimately, Australians with HIV may benefit directly from anti-HIV compounds produced and may also benefit from advances in our understanding of this elusive virus resulting from the project.Read moreRead less
The geometry of genome access: lessons from HIV. Access to the cell’s nucleus, and hence its genome, is of deep scientific and commercial significance. It is controlled by a phase-separated diffusion barrier within the nuclear pore complex. Recent evidence, however, has shown that HIV can cross this barrier with its protective capsid intact, despite it being over one thousand times larger than the limit for passive transport. Combining concepts from soft-matter physics with recombinant assays, t ....The geometry of genome access: lessons from HIV. Access to the cell’s nucleus, and hence its genome, is of deep scientific and commercial significance. It is controlled by a phase-separated diffusion barrier within the nuclear pore complex. Recent evidence, however, has shown that HIV can cross this barrier with its protective capsid intact, despite it being over one thousand times larger than the limit for passive transport. Combining concepts from soft-matter physics with recombinant assays, this project aims to uncover the link between the unique geometry of HIV capsids and their ability to subvert the nucleus’ defenses. The expected outcome is a step-change in the understanding of nuclear access control, with downstream benefits to virology, bio-engineering and bio-technology.Read moreRead less
Maintaining fidelity in viral Ribonucleic acid (RNA) polymerases. This project will provide informed insights into the dynamics of viruses that currently impact a healthy start to life, ageing well and productively, and preventative healthcare. The analysis of viruses that cause gastroenteritis outbreaks will increase our understanding of how these viruses replicate and spread.
Virulence determinants influencing re-emergence of a complex RNA virus. This project intends to examine the effects that specific genes in naturally occurring recombinants have on their capacity to cause disease and spread between chickens. Coronaviruses are major pathogens of domestic animals throughout the world. Recurrent re-emergence of the coronavirus of chickens, infectious bronchitis virus, has been associated with recombination between wild type viruses and vaccine viruses, but the facto ....Virulence determinants influencing re-emergence of a complex RNA virus. This project intends to examine the effects that specific genes in naturally occurring recombinants have on their capacity to cause disease and spread between chickens. Coronaviruses are major pathogens of domestic animals throughout the world. Recurrent re-emergence of the coronavirus of chickens, infectious bronchitis virus, has been associated with recombination between wild type viruses and vaccine viruses, but the factors influencing this, and in particular the selective advantages genes from vaccine viruses confer on these recombinants, are unknown. The ultimate aim of the project is to identify both novel vaccines and alternative management strategies that might reduce the frequency of re-emergence of this virus and other coronaviruses.Read moreRead less
Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis a ....Noncoding RNAs of insect-specific flaviviruses: biogenesis and functions. This project aims to investigate noncoding RNAs (sfRNAs) of insect-specific flaviruses (ISFs). These RNAs are produced from viral RNA by host ribonuclease and play important role in pathogenesis and transmission of vertebrate-infecting flaviviruses (VIFs). The team has shown that ISFs also produce sfRNAs although likely employing a different mechanism. The project expects to generate new knowledge on ISF sfRNA biogenesis and functions using combination of modern structural, biochemical, and innovative molecular virology methods. The outcome will be a clearer understanding of processes governing flavivirus host restriction and evolution. This will improve understanding of virus-host interactions and train students in cutting edge techniques.Read moreRead less
Avoiding the immune response: lessons from 'simple' bacteria. Some of the most important bacterial diseases of domestic animals are caused by mycoplasmas. Improved control of these diseases would significantly improve agricultural productivity by reducing losses associated with reduced feed conversion efficiency and increased susceptibility to other diseases, as well as improve animal welfare and public health, by reducing the need for antibiotic therapy to control these diseases in food produci ....Avoiding the immune response: lessons from 'simple' bacteria. Some of the most important bacterial diseases of domestic animals are caused by mycoplasmas. Improved control of these diseases would significantly improve agricultural productivity by reducing losses associated with reduced feed conversion efficiency and increased susceptibility to other diseases, as well as improve animal welfare and public health, by reducing the need for antibiotic therapy to control these diseases in food producing animals.Read moreRead less