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How class of drugs blocks Hepatitis C virus replication

Findings reveal a difference between strains of HCV

Date:
June 8, 2017
Source:
University of North Carolina Health Care
Summary:
For the first time, researchers show how the antiviral class of drugs called NS5A inhibitors interacts with the hepatitis C virus, and these findings show a difference between strains of HCV.
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Globally, an estimated 71 million people are living with chronic hepatitis C virus (HCV). Over decades of infection, chronic HCV infection results in progressive damage to the liver and an increased risk for end stage liver disease and liver cancer, making the virus the leading cause of liver-related deaths in the United States today.

While effective combination therapies have recently been developed, HCV can evolve to become resistant to these antiviral drugs, potentially resulting in treatment failures. Resistance is particularly important for one class of medications used in treatment, for which the mechanism by which it stops growth of the virus is poorly understood. For the first time, researchers at the University of North Carolina at Chapel Hill have identified how the class of antiviral drugs known as NS5A inhibitors interacts with the virus, and their findings show a difference between strains of HCV. These results were published in PLOS Pathogens.

"When HCV infects a liver cell, it establishes replication complexes (RCs) within the cell," said David McGivern, Ph.D., lead-author and an associate professor in the UNC Division of Infectious Diseases. "These may be thought of as factories that replicate the virus genetic material. We wanted to understand how long these factories persist in an infected cell after treatment with an NS5A inhibitor."

The research team has shown previously NS5A inhibitors block the formation of new RCs, but do not affect existing RCs, which are ultimately lost from the cell during treatment. The team used NS5A inhibitors to estimate the half-life of the existing RCs and found a difference in the speed of decline depending upon the strain of HCV.

"The majority of people who undergo antiviral treatment clear their HCV infection," said McGivern. "But about 5 percent of people experience treatment failure, often associated with drug resistance. Our findings have potentially important implications for this group of people. Did the treatment fail because replication complexes turned over more slowly? Do some strains of HCV need longer treatment? A better understanding of these issues may lead to more effective therapies active against a broader range of viruses."


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Materials provided by University of North Carolina Health Care. Note: Content may be edited for style and length.


Journal Reference:

  1. Tiffany Benzine, Ryan Brandt, William C. Lovell, Daisuke Yamane, Petra Neddermann, Raffaele De Francesco, Stanley M. Lemon, Alan S. Perelson, Ruian Ke, David R. McGivern. NS5A inhibitors unmask differences in functional replicase complex half-life between different hepatitis C virus strains. PLOS Pathogens, 2017; 13 (6): e1006343 DOI: 10.1371/journal.ppat.1006343

Cite This Page:

University of North Carolina Health Care. "How class of drugs blocks Hepatitis C virus replication." ScienceDaily. ScienceDaily, 8 June 2017. <www.sciencedaily.com/releases/2017/06/170608202150.htm>.
University of North Carolina Health Care. (2017, June 8). How class of drugs blocks Hepatitis C virus replication. ScienceDaily. Retrieved May 19, 2024 from www.sciencedaily.com/releases/2017/06/170608202150.htm
University of North Carolina Health Care. "How class of drugs blocks Hepatitis C virus replication." ScienceDaily. www.sciencedaily.com/releases/2017/06/170608202150.htm (accessed May 19, 2024).

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