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
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.
Molecular Characterization Of Dengue Virus Fusion And Antiviral Inhibitors.
Funder
National Health and Medical Research Council
Funding Amount
$573,557.00
Summary
Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries around the world, including Australia. Infection with dengue viruses cause severe and sometimes fatal disease. This proposal focuses on the way dengue virus enters cells and the development of drugs that will prevent virus entry. We have already identified compounds that inhibit the entry process of dengue into cells and this project will significantly build on these early findings.
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.
Forecasting The Impact Of Climate Change On Dengue Transmission
Funder
National Health and Medical Research Council
Funding Amount
$506,432.00
Summary
Dengue fever (DF) is the most important mosquito-transmitted viral disease in the world. The large-scale re-emergence of DF in the Asia-Pacific region during the past few decades has renewed its status as a serious international public health problem. Global climate change is anticipated to impact upon the biology and ecology of vectors and consequently the risk of DF transmission. The principal research aim of this study is to project the impact of future climate change on DF.
Investigation Of The Optimal Assessment Of Febrile Passengers Detected By Infrared Thermal Scanning At An Int'l Airpor
Funder
National Health and Medical Research Council
Funding Amount
$166,587.00
Summary
The aim of this project is to establish an evidence-based approach to business preparedness for pandemic influenza. We will identify key areas of vulnerability in small and medium-sized businesses which can be targeted to enhance preparedness for pandemic influenza, and thus contribute to control of the spread of pandemic influenza in the community.
Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries in tropical and subtropical regions. Infection with Dengue viruses cause Dengue fever or its more severe and sometimes fatal form, Dengue hemmorrhagic fever-Dengue shock syndrome (DHF-DSS). Up to 100 million people are infected annually making Dengue virus one of the most important and frequent mosquito-borne viral diseases worldwide. Over the past two decades, the incidence of Dengue virus infectio ....Dengue viruses are transmitted by mosquitoes and cause major epidemics in more than 100 countries in tropical and subtropical regions. Infection with Dengue viruses cause Dengue fever or its more severe and sometimes fatal form, Dengue hemmorrhagic fever-Dengue shock syndrome (DHF-DSS). Up to 100 million people are infected annually making Dengue virus one of the most important and frequent mosquito-borne viral diseases worldwide. Over the past two decades, the incidence of Dengue virus infection has increased steadily. More than 40% of the world's population is at risk of infection and this number is expected to increase as more people travel. This proposal focuses on the way dengue virus enters cells, specifically the mechanism used by viral proteins to mediate fusion of the viral membrane with that of the host cell. A clearer understanding of the molecular basis of this process should provide potential targets for new drugs that can bind and block this process. In addition, we will also use this information in the design and generation of new vaccine candidates.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
The Interactions Of Dengue Virus RNA Dependent RNA Polymerase (NS5) With Other Viral And Host Factors.
Funder
National Health and Medical Research Council
Funding Amount
$170,165.00
Summary
Dengue fever is a mosquito-borne disease that is prevalent in tropical countries. It is estimated that 40% of the global population is at risk of dengue infection. Classical dengue fever is not life threatening. However, the more serious disease, dengue haemorrhagic fever-shock syndrome requires intensive medical attention to prevent fatality. A significant number of deaths are recorded each year especially in the underdeveloped countries. Dengue is periodically also a problem in northern Austra ....Dengue fever is a mosquito-borne disease that is prevalent in tropical countries. It is estimated that 40% of the global population is at risk of dengue infection. Classical dengue fever is not life threatening. However, the more serious disease, dengue haemorrhagic fever-shock syndrome requires intensive medical attention to prevent fatality. A significant number of deaths are recorded each year especially in the underdeveloped countries. Dengue is periodically also a problem in northern Australia. There is no cure for dengue fever. The present research aims to use a knowledge-based approach to develop novel antiviral strategies based on preventing the critical protein interactions required for the normal virus life cycle. Two of the most important proteins involved in dengue virus replication are called the NS3 and NS5 proteins. The protein-protein interaction (contact) that occurs between NS5 and NS3 is crucial for the replication of the virus. Little is known about this interaction at present, and the studies we propose will directly address this issue. We have previously shown that a 37 amino acid in the middle of NS5 contains a nuclear localisation signal that can target the normally cytoplasmic protein to the nucleus of the infected cell. What the function of this protein is in the nucleus is not known. We will use a technique called the yeast two-hybrid test to address the question of dengue virus protein interactions in the common bakers yeast. This method is very sensitive and powerful and will provide important insights that will contribute to the development of a rapid high-throughput test to screen the extensive extract collection from Australia's marine biodiversity, held by the Australian Institute of Marine Sciences, to discover suitable inhibitors of NS3-NS5 interaction.Read moreRead less