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Discovering Dengue Drugs – Together |
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Project Status and Findings:
Information about this project is provided on the web pages below and by the project scientists on the Discovering Dengue Drugs - Together website. For the latest status report, please go to the Discovering Dengue Drugs - Together status report. If you have comments or questions about this project, please visit the Discovering Dengue Drugs – Together forum.
Mission
The mission of Discovering Dengue Drugs – Together is to identify promising drug leads to combat the related dengue, hepatitis C, West Nile, and Yellow fever viruses. The extensive computing power of World Community Grid will be used to complete the structure-based drug discovery calculations required to identify these leads.
Significance
This project will discover promising drug leads that stop the replication of viruses within the Flaviviridae family. Members of this family, including dengue, hepatitis C, West Nile, and Yellow fever viruses, pose significant health threats throughout the developed and developing world. More than 40% of the world's population is at risk for infection by dengue virus. Annually, 1.5 million people are treated for dengue fever and dengue hemorrhagic fever. Hepatitis C virus has infected ~2% of the world's population. Yellow fever and West Nile viruses have also had significant global impact. Unfortunately, there are no drugs that effectively treat these diseases. Consequently, the supportive care necessary to treat these infections and minimize mortality severely strains already burdened health facilities throughout the world. The discovery of both broad–spectrum and specific antiviral drugs is expected to significantly improve global health.
Approach
One promising approach to combat these viruses and prevent them from causing disease is to develop drugs that inhibit the viral NS3 protease. The NS3 protease is an enzyme critical for virus replication, and its amino acid sequence and atomic structure are very similar among the different disease–causing flaviviruses. Since the atomic structure of the NS3 protease is known, we can utilize advanced structure–based computational drug discovery methods to identify small molecule protease inhibitors.
Dr. Stan Watowich and his research team at The University of Texas Medical Branch (Galveston, Texas, USA) have made significant progress in this direction, having discovered compounds that inhibit dengue and West Nile virus proteases and prevent virus replication in cell culture. However, additional drug candidates need to be discovered to improve the likelihood of converting drug leads into approved drugs for treating flavivirus infections.
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