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Project Summary: Viruses from the family Flaviviridae, such as dengue (DENV), hepatitis C (HCV), West Nile (WNV), and yellow fever (YFV) 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 DENV. Annually, 1.5 million people are treated for dengue fever and dengue hemorrhagic fever. In addition, ~2% of the world’s population is infected with HCV. Yellow fever and West Nile viruses have also had significant global impact. Unfortunately, there are no drugs that effectively treat these diseases.
One promising approach to combat these diseases is to develop drugs that inhibit the viral protease. This enzyme is critical for virus replication and is highly conserved among different flaviviruses. We have already made significant progress, having successfully identified compounds that simultaneously inhibit DENV and WNV 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.
The computing power of World Community Grid will be harnessed to complete calculations that will identify new compounds that bind tightly to flavivirus proteases, and terminate DENV, HCV, WNV, and YFV replication. Normally, these calculations require thousands of years of computer time. However, the combined power of World Community Grid computers will enable this project to be completed within 9-12 months.
Identifying new compounds that broadly inhibit dengue, hepatitis C, West Nile, and yellow fever viruses is a significant step in our quest to change the world by dramatically improving global health.
The mission of this project is to identify drug leads with broad spectrum activity against 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 promising drug leads.