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
Chikungunya Virus Disease; The Role Of Proteases And Their Receptors
Funder
National Health and Medical Research Council
Funding Amount
$682,716.00
Summary
Chikungunya virus (CHIKV) is a mosquito borne virus related to the Australian Ross River virus. The arthritic disease caused by these viruses is often poorly managed by current treatments. We have recently identified several proteins call proteases that circulate in the blood of infected people and promote arthritis. If successful the grant will provide new treatment options for these (and perhaps other) diseases using recently developed drugs that inhibit the activity of these proteases.
Activation Of The Respiratory Syncytial Virus Fusion Protein
Funder
National Health and Medical Research Council
Funding Amount
$582,072.00
Summary
Respiratory Syncytial Virus (RSV) is the most important viral cause of respiratory tract disease in both infants and the elderly. However, there are few available options for control, whether by vaccination or therapeutic intervention. This proposal investigates the way RSV infects cells. A clearer understanding of the molecular basis of this process should provide potential targets for new drugs that can block this process and new insights for the generation of vaccine candidates.