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.
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
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.