To understand how Hendra virus multiplies in infected cells, we will investigate the structure of its replicative machinery. This will provide the basis for rational drug design increasing Australia’s preparedness against the emergence of Hendra-like viruses.
Structural Characterization Of A Novel AB5 Cytoxin - SubAB
Funder
National Health and Medical Research Council
Funding Amount
$210,760.00
Summary
The proposed research program, using a combinantion of structural biology and biophysical techniques will provide insight into the role of novel AB5 toxin from E. coli. This study will not only improve our fundamental understanding the mode of action of this toxin from this devastating pathogen, but could lead to the design of rational antimicrobials. The knowledge gained will increase Australian international research profile.
Design And Development Of Inhibitors Of The Dengue Virus Protease As Antiviral Drugs
Funder
National Health and Medical Research Council
Funding Amount
$362,513.00
Summary
Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This proposal focuses on a virus specific enzyme. This enzyme (called a protease) is es ....Dengue viruses are carried by mosquitoes and infect millions of people around the world, particularly in tropical countries of SE Asia, Central and South America, Africa and recently in Australia (North Queensland and NT). There is no vaccine or drug available for preventing or treating the infections, which are characterised by severe illness that involves inflammation and fevers that can sometimes be fatal. This proposal focuses on a virus specific enzyme. This enzyme (called a protease) is essential for the virus to multiply and so it is a potential target for new drugs that can bind to it and block its function. We have produced and purified this viral enzyme in the laboratory and now propose to design, synthesize, and develop the first drugs for the treatment of humans infected with dengue virus. We plan to do this by examining the action of the enzyme, determining its three dimensional structure, and using computers and chemical methods to obtain very powerful blockers of enzyme action. These drug candidates will be tested against the enzyme, against cells infected with virus, and in rats to find out if they can be administered by mouth or by injection and if they have any toxic side effects. This project will provide valuable information about how to develop drugs to stop dengue fever and its associated illnesses.Read moreRead less
Understanding Novel Viral Host Interactions That Modulate Innate Immunity
Funder
National Health and Medical Research Council
Funding Amount
$764,246.00
Summary
Lethal viruses such as coronaviruses (MERS, SARS-CoV-1, SARS-CoV-2), Dengue, Zika, Hendra, and Nipah have developed effective mechanisms of replication by dampening the host immune system. Here we will examine how viruses carry out these immune evasion functions, and test antiviral drugs that can prevent these effects in a highly specific manner. If this idea can be proved, it will provide great promise for the development of new antivirals whilst minimising the toxic effects to the cell.
Understanding Cell Signalling As A Basis For New Therapeutics
Funder
National Health and Medical Research Council
Funding Amount
$2,231,372.00
Summary
This Investigator grant will capitalise on my extensive expertise in determining the three-dimensional atomic structures of proteins to uncover fundamental biological mechanisms in cancer and Alzheimer’s disease as a basis for discovering new drugs to combat these devastating diseases.