Dengue fever is a debilitating tropical disease that threatens 40 percent of the world’s population. As part of World Community Grid’s 10th anniversary celebrations, research partner Stan Watowich, Ph.D., talks about how the program enabled his team to identify a new drug lead that could stop the virus in its tracks.
Dengue fever, also known as “breakbone fever”, causes excruciating joint and muscle pain, high fever and headaches. Severe dengue, known as “dengue hemorrhagic fever”, has become a leading cause of hospitalization and death among children in many Asian and Latin American countries. According to the World Health Organization, more than 40 percent of the world’s population is at risk from dengue – with one study estimating that there were 390 million cases in 2010 alone. The mosquito-borne infectious disease is found in tropical and sub-tropical regions primarily in the developing world, and belongs to the flavivirus family of viruses, together with Hepatitis C, West Nile and Yellow Fever.
Although dengue represents a critical global health concern, it has received limited attention from affluent countries until recently, and is widely considered to be a neglected tropical disease. Since no approved vaccines or treatments exist for the disease, we launched Discovering Dengue Drugs – Together on IBM’s World Community Grid in 2007 – using a computer-based discovery approach to search for drugs to treat dengue infections.
In the first phase of the project, we sought to identify compounds that could be used to develop dengue-fighting drugs. Thanks to the computing power donated by World Community Grid volunteers, my fellow researchers and I at The University of Texas Medical Branch at Galveston screened around three million chemical compounds to determine which ones would bind to the dengue virus and disable it. By 2009, we had found several thousand promising compounds to take to the next stage of testing, and began identifying the strongest of those compounds with the goal of turning them into molecules suitable for human clinical trials.
Insights from our Discovering Dengue Drugs study recently have led to an exciting discovery. Using findings from the study to guide additional calculations on DrugDiscovery@TACC – our web portal for advanced computer-based drug discovery – we have identified a molecule that has demonstrated success in binding to, and disabling, a key dengue enzyme that is necessary for replication of the virus. This molecule also shows signs of being able to disable related flaviviruses (such as the West Nile virus) without negative side effects. We are working with medicinal chemists to synthesize variants of this exciting candidate molecule for investigation in pre-clinical and clinical trials.
None of these advances would have been possible without the dedication of World Community Grid volunteers, who contributed the unused computing power of their desktop and mobile devices for our use. We owe the progress we are making – and our improved understanding of drug discovery software and its current limitations – to your commitment to supporting humanitarian research.
If you’d like to help researchers make more ground-breaking discoveries like this, join World Community Grid today to start donating your unused computing power to cutting-edge research on global health, poverty and sustainability solutions.
Stan Watowich, Ph.D., is the lead researcher for the Discovering Dengue Drugs – Together project and Associate Professor in the Department of Biochemistry and Molecular Biology at The University of Texas Medical Branch (UTMB) at Galveston. Dr. Watowich was a founding member of UTMB’s renowned Sealy Center for Structural Biology, and launched UTMB’s Molecular Therapeutics Initiative. He also serves as a consultant for drug discovery projects in developing countries.
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