Nuclear Functions Of Dengue NS5 Protein: Role In Disease
Funder
National Health and Medical Research Council
Funding Amount
$736,953.00
Summary
Our work indicates that the NS5 protein from Dengue virus (DV) has distinct sequences that enable it to traffic into and out of the host cell nucleus to exert pathogenic effects on transcription and thereby impair the host cell anti-viral and immune responses. We aim to characterise these properties in detail, and demonstrate their importance to DV pathogenicity using a novel animal model of the disease.
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
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