Inhibitors Of West Nile Virus Protease As Antiviral Drugs
Funder
National Health and Medical Research Council
Funding Amount
$590,740.00
Summary
The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in people i ....The West Nile Virus (WNV) was first isolated from a woman in the West Nile region of Uganda in 1937. It is one of ~70 known flaviviruses (e.g. Dengue fever, Yellow fever, West Nile, Kunjun, Japanese encephalitis, St. Louis encephalitis, tick-borne encephalitis, Australian encephalitis and the related hepatitis C virus) which annually infect hundreds of millions of people worldwide, particularly in tropical and sub-tropical areas, and cause major public health problems. WNV is endemic in people in the Middle East, parts of Africa and Europe, but recent epidemics in Israel (1998), Romania (1996), United States (1999), and UK (2003), that have been traced to migratory birds, were characterized by severe symptoms , severe neurological pathology, and fatalities. In the USA alone there were 4,156 infections and 284 deaths in 2002, 9122 infections and 223 deaths in 2003, and this mosquito borne virus has quickly spread since 1999 through all USA states and into Canada and Mexico (http:--www.cdc.gov-ncidod-dvbid- westnile-index.htm). No treatments or vaccines are available. This project focuses on a viral enzyme, known as the West Nile Virus NS3 protease, that is essential for replication of the virus. By studying the enzyme in the laboratory we can design small molecules that block its function and these are potential leads for developing drug treatments for people infected, not only by this virus but potentially also other flaviviruses. A precedent is the success of inhibitors of HIV-1 protease that are the most effective treatment for humans with HIV-infections, and other viral proteases are now becoming recognized as viable antiviral targets for pharmaceutical development. The project involves experts on small molecule protease inhibitor design and development, proteases, and virology including West Nile virology. We expect to generate new information at the cutting edge of West Nile Virus and flavivirus research and promising new antiviral drug candidates.Read moreRead less
Hepatitis B Virus Drug Resistance: Impact On The Immunisation Program
Funder
National Health and Medical Research Council
Funding Amount
$113,322.00
Summary
ñAntiviral drug-associated vaccine escape mutantsî have the potential to jeopardize the hepatitis B immunization program. Which particular viral mutations or combination of mutations that can directly affect the clinical outcome of infection, especially in the context of vaccine induced immunity, are not known. In this study we will identify the clinical sequelae and public health consequences arising from the selection of these mutants.
A Universal Prophylactic Vaccine For Hepatitis C Virus
Funder
National Health and Medical Research Council
Funding Amount
$643,337.00
Summary
Hepatitis C Virus (HCV) infects 200 million people world wide. An effective vaccine to prevent HCV is urgently needed but must afford protection against the 7 diverse genotypes. In this project grant we aim to further define the quality of the immune response that is generated by a novel HCV vaccine candidate that generates pan-genotypic immunity, its unique structural features, and methods of manufacturing so that it can be tested in a future phase I human clinical trial.
Viral Targeting Of STAT Proteins: Roles In Disease
Funder
National Health and Medical Research Council
Funding Amount
$536,985.00
Summary
The capacity of viruses to evade the host immune response is critical to the development of disease. We recently showed that interaction of specific viral proteins with host immune proteins called STATs is vital to lethal disease caused by lyssaviruses. In this project, we aim to define in detail the functions of these interactions in viral modification of host biology and evasion of the immune response, and to use this information to develop new vaccines against highly pathogenic human viruses.
The Role Of Capsid Protein Nucleolar Localisation In Chikungunya Virus: Implications For Vaccine Development
Funder
National Health and Medical Research Council
Funding Amount
$520,520.00
Summary
Chikungunya virus (CHIKV) is a globally widespread mosquito-borne alphavirus capable of causing considerable human morbidity and mortality. With no CHIKV vaccine or antiviral available this proposal aims to develop a live attenuated CHIKV vaccine, rationally designed by investigating the host cell nucleolar trafficking of CHIKV capsid protein. This vaccine has the potential to provide cross-protection against additional arthritogenic alphaviruses endemic to Australia such as Ross River virus.
Dengue virus is the most important mosquito-borne viral disease, with 2/3 of the world's population at risk. There is currently no treatment available for dengue. Our proposal aims to progress a safe and effective new treatment (4-HPR) against Dengue towards the clinic, generating all the required pharmacokinetic and pre-clinical animal data necessary to progress to a future clinical trial in humans. We will also investigate the use of 4-HPR as a dengue preventative.
Novel Antivirals For The Treatment Of Hendravirus Infection.
Funder
National Health and Medical Research Council
Funding Amount
$199,227.00
Summary
Hendravirus outbreaks have become frequent and 7 human cases have been reported, this has resulted in 4 deaths. Currently we have no treatment options. Researchers at Griffith University and the CSIRO have developed a new treatment that attacks the virus by turning off the viral genes at the site of infection. The plan is to treat patients soon after infection to slow or stop the virus and allow patients to recover naturally from this highly lethal disease.
Determining The Clinical Effectiveness Of Antiviral Drugs Against Oseltamivir- And Laninamivir-resistant Influenza Viruses In Animal Models
Funder
National Health and Medical Research Council
Funding Amount
$388,067.00
Summary
Currently, the neuraminidase inhibitors are the only drugs that are effective against seasonal influenza viruses. However, viruses can develop resistance to these drugs. Using viruses with varied levels of resistance, the project will determine the effectiveness of different drug treatments in animal models. This will lead to better treatment for those patients seriously ill with drug-resistant influenza viruses.
Combining Laboratory And Computational Approaches To Develop Reliable Low Cost HIV Prognostics
Funder
National Health and Medical Research Council
Funding Amount
$314,644.00
Summary
Certain anti-HIV drugs called "CCR5 antagonists" block HIV entry into immune cells. However, HIV drug-resistance can occur. Globally, patient access to CCR5 antagonists has been limited because the pre-treatment laboratory test required to determine HIV drug-resistant is expensive and time-consuming. My research will lead to development of computer programs that reliably, rapidly and cheaply determine HIV drug-resistance and thus greatly improve patient access to CCR5 antagonists worldwide.