Scientists map key protein structure of Hepatitis C virus

A team led by scientists at Scripps Research and the University of Amsterdam has achieved an important goal in virology: mapping, at high resolution, critical proteins that stud the surface of the Hepatitis C virus (HCV) and enable it to enter host cells.

The discovery, reported in Science on October 21, 2022, details key sites of vulnerability on the virus — sites that can now be targeted effectively with vaccines.

“This long sought-after structural information on HCV puts a wealth of previous observations into a structural context and paves the way for rational vaccine design against this incredibly difficult target,” says study co-senior author Andrew Ward, PhD, professor in the Department of Integrative Structural and Computational Biology at Scripps Research.

The study was the product of a multi-year collaboration that included the Ward laboratory, the lab of Gabriel Lander, PhD (also a professor in the Department of Integrative Structural and Computational Biology at Scripps Research); the lab of Rogier Sanders, PhD, of the University of Amsterdam; and the lab of Max Crispin, DPhil, at the University of Southampton.

It is projected that roughly 60 million people globally — including about two million Americans — have chronic HCV infections. The virus infects liver cells, typically establishing a “silent” infection for decades until liver damage becomes severe enough to cause symptoms. It is a leading cause of chronic liver disease, liver transplants and primary liver cancers.

The origins of the virus are uncertain, but it is thought to have emerged at least several hundred years ago, and then eventually spread globally — especially via blood transfusions — in the latter half of the 20th century. While the virus was mostly eliminated from blood banks after its initial discovery in 1989, it continues to spread chiefly via needle-sharing among intravenous drug users in developed countries, and by the use of unsterilized medical instruments in developing countries. The leading HCV antiviral drugs are effective but far too expensive for large-scale treatment.

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