Scientists at Scripps Research and the University of Amsterdam got a stupendous achievement in the field of virology. They mapped, with high resolution, key protein structures that stud the surface of the Hepatitis C virus (HCV), which enable it to enter host cells.
The key finding by the researchers, reported in Science on October 21, 2022, have detailed major sites of vulnerability on the virus, which can now be targeted effectively with vaccines, reported ANI.
The much sought-after discovery regarding structural information on HCV puts a wealth of previous observations into a structural context, which paves the way for rational vaccine design against the 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 research was the amalgamation of a several-year collaboration which 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 estimated that around 60 million people across the world, including nearly two million Americans, are suffering from the chronic HCV infections. The virus infects liver cells silently, and symptoms appear after the liver damage becomes severe enough, which leads to chronic liver disease, liver transplants and primary liver cancers.
It is thought the virus emerged at least several hundred years ago, which eventually spread across the world, especially through blood transfusions, in the latter half of the 20th century.
Although the virus was mostly removed from blood banks after its discovery in 1989, it has spread mainly through needle-sharing among intravenous drug users in developed countries, and by the use of unsterilized medical instruments in developing countries. The HCVHepatitis C virus antiviral drugs are effective, but they are quite expensive for large-scale treatment.
An effective vaccine could potentially remove HCV as a public health burden. However, scientists have not developed such a vaccine because of huge difficulty in researching HCV’s envelope protein complex, which is made of two viral proteins called E1 and E2, ANI reported.
“The E1E2 complex is very flimsy — it’s like a bag of wet spaghetti, always changing its shape — and that’s why it’s been extremely challenging to image at high resolution,” says co-first author Lisa Eshun-Wilson, PhD, a postdoctoral research associate in both the Lander and Ward labs at Scripps Research.
According to the researchers, they could use a combination of three neutralizing anti-HCV antibodies to stabilize the E1E2 complex in a natural conformation. Neutralizing antibodies may enable to protect against a broad range of viral strains, by binding to relatively non-varying sites on the virus in ways that interrupt the viral life cycle.
The researchers imaged the antibody-stabilized protein complex using low-temperature electron microscopy. The scientists were able to generate an E1E2 structural map of unprecedented clarity and extent with the help of advanced image-analysis software.