|By: Dr. Stan Watowich, PhD|
|University of Texas Medical Branch (UTMB) in Galveston, Texas|
|10 Nov 2014|
For week five of our decade of discovery celebrations we’re looking back at the Discovering Dengue Drugs - Together project, which helped researchers at the University of Texas Medical Branch at Galveston search for drugs to help combat dengue - a debilitating tropical disease that threatens 40% of the world’s population. Thanks to World Community Grid volunteers, researchers have identified a drug lead that has the potential to 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 (WHO), over 40% of the world’s population is at risk from dengue; another study estimated there were 390 million cases in 2010 alone.
The disease is a mosquito-borne infection found in tropical and sub-tropical regions - primarily in the developing world. It belongs to the flavivirus family of viruses, together with Hepatitis C, West Nile and Yellow Fever.
Despite the fact 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. Currently, no approved vaccines or treatments exist for the disease. We launched Discovering Dengue Drugs - Together on World Community Grid in 2007 to search for drugs to treat dengue infections using a computer-based discovery approach.
In the first phase of the project, we aimed to identify compounds that could be used to develop dengue drugs. Thanks to the computing power donated by World Community Grid volunteers, my fellow researchers and I at the University of Texas Medical Branch in Galveston, Texas, 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. We began identifying the strongest compounds from the thousands of potentials, with the goal of turning these into molecules that could be suitable for human clinical trials.
We have recently made an exciting discovery using insights from Discovering Dengue Drugs - Together to guide additional calculations on our web portal for advanced computer-based drug discovery, DrugDiscovery@TACC. A molecule has demonstrated success in binding to and disabling a key dengue enzyme that is necessary for the virus to replicate.
Furthermore, it also shows signs of being able to effectively disable related flaviviruses, such as the West Nile virus. Importantly, our newly discovered drug lead also demonstrates no negative side effects such as adverse toxicity, carcinogenicity or mutagenicity risks, making it a promising antiviral drug candidate for dengue and potentially other flavivirues. We are working with medicinal chemists to synthesize variants of this exciting candidate molecule with the goal of improving its activity for planned pre-clinical and clinical trials.
I’d like to express my gratitude for the dedication of World Community Grid volunteers. The advances we are making, and our improved understanding of drug discovery software and its current limitations, would not have been possible without your donated computing power.
If you’d like to help researchers make more ground-breaking discoveries like this - and have the chance of winning some fantastic prizes - take part in our decade of discovery competition by encouraging your friends to sign up to World Community Grid today. There’s a week left and the field is wide open - get started today!
Here’s to another decade of discovery.