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
GPI Anchored Forms Of The Dengue Virus NS1 Protein: Production And Role In Pathogenesis
Funder
National Health and Medical Research Council
Funding Amount
$203,448.00
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 study focuses on an unusual form of a dengue virus protein (called NS1) which we h ....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 study focuses on an unusual form of a dengue virus protein (called NS1) which we have identified. We plan to study the role that this protein plays in the more severe and often fatal forms of dengue infection (dengue haemorrhagic fever and dengue shock syndrome). In these more severe and life threatening forms of dengue the blood vessels of these patients become leaky. It is thought that this is caused by the secretion of certain chemicals (cytokines) from infected cells. We have shown that dengue infected human cells, which have the unusual form of NS1 protein on their surface, are capable of being activated by antibodies. Antibodies are proteins which are produced by the human body to fight infection. We aim to study whether cytokines are secreted from infected human blood cells activated in this way and whether these cytokines cause blood vessels to become leaky. We will also study how the virus produces this variant form of NS1 in the two host species that the virus infects; mosquito and human. These studies will increase our understanding of dengue virus infection and will provide valuable information concerning the role that this unusual form of the degue virus protein NS1 plays in the severe forms of dengue fever; dengue haemorrhagic fever and dengue shock syndrome.Read moreRead less
Determination Of Disease Specific Epitopes In Rheumatic Heart Disease In Australia
Funder
National Health and Medical Research Council
Funding Amount
$374,817.00
Summary
Rheumatic Fever and Rheumatic Heart Disease (RF-RHD) remain a significant cause of illness in Aboriginal communities in Australia. RF-RHD is a complication which follows infection with a specific bacterium. The purpose of this study is to compare the body's response and find out the patterns of antibody and immune cell reactivity to the bacterium and body proteins in RF-RHD patients and controls. It will also enable us to study the mechanisms that initiate the disease process.
Despite advances in medical management, critical care clinicians continue to search for procedures that will improve outcomes in critically ill patients with haemorrhagic shock (a life-threatening fall in blood pressure). Shock is a consequence of an active process triggered by the brain . The proposed research aims to elucidate the precise sequence of brain events that initiate and maintain shock. We will also evaluate the effects of interventions (designed to ameliorate or reverse shock) on th ....Despite advances in medical management, critical care clinicians continue to search for procedures that will improve outcomes in critically ill patients with haemorrhagic shock (a life-threatening fall in blood pressure). Shock is a consequence of an active process triggered by the brain . The proposed research aims to elucidate the precise sequence of brain events that initiate and maintain shock. We will also evaluate the effects of interventions (designed to ameliorate or reverse shock) on the brain events that drive the shock response. The results of this research will offer, for the first time, a rational basis for devising new methods to reverse or ameliorate shock and potentially improve clinical outcomesRead moreRead less
Identification Of Molecular And Cellular Pathways Predicting Susceptibility Or Resistance To Severe Dengue Fever
Funder
National Health and Medical Research Council
Funding Amount
$761,481.00
Summary
This cooperative research project aims to undertake a comprehensive immunological and molecular analysis of individuals with mild versus severe dengue fever recruited at local hospitals in Jakarta, Indonesia. The project will uncover key processes responsible for the development of severe disease. This information will identify specific biomarkers for innovative diagnostic tools for early prediction/detection of cases that will progress to complicated dengue.
Modelling The Impact Of Global Climate Change On The Epidemiology Of Infectious Diseases In Bangladesh
Funder
National Health and Medical Research Council
Funding Amount
$118,988.00
Summary
Climate change may impact on human health via a change in the distribution and pathogenicity of infectious diseases, particularly in the South Asian region. This study will use high quality environmental and clinical data from an established time-series collated in Bangladesh, to better inform mathematical models which may predict future changes in infectious diseases epidemiology. Accurate and valid modelling can be valuable in guiding future public health policy for vulnerable populations.
Australian Predicting Infectious ComplicatioNs In Children With Cancer (PICNICC) Project
Funder
National Health and Medical Research Council
Funding Amount
$694,980.00
Summary
Children undergoing cancer treatment are at an increased risk of infection. This is managed by admission to hospital for antibiotics which can be a frightening experience for the child, disruptive for their family and expensive for the healthcare system. While many need admission, a proportion of patients can be safely managed at home with oral or intravenous antibiotics. This project aims to identify these children, so as to improve their quality of life, and decrease cost of treatment.