Scientists Discover Key to Hepatitis A Virus Replication, Show Drug Effectiveness With no current treatments for hepatitis A, scientists at the University of North Carolina School of Medicine led by Stanley M. Lemon, MD, discovered how a protein and enzymes interact to allow hepatitis A virus to pr
in 2019 was linked to fresh blackberries. Globally, tens of millions of HAV infections occur each year. Symptoms include fever, abdominal pain, jaundice, nausea, and loss of appetite and sense of taste. Once sick, there is no treatment.
A few years ago, researchers found that hepatitis B virus required TENT4A/B for its replication. Meanwhile, Lemon’s lab led experiments to search for human proteins that HAV needs in order to replicate, and they found ZCCHC14 – a particular protein that interacts with zinc and binds to“This was the tipping point for this current study,” Lemon said. “We found ZCCHC14 binds very specifically to a certain part of HAV’s RNA, the molecule that contains the virus’s genetic information.
This work suggested that stopping TENT4 recruitment could stop viral replication and limit disease. Lemon’s lab then tested the compound RG7834, which had previously been shown to actively block Hepatitis B virus by targeting TENT4. In thepaper, the researchers detailed the precise effects of oral RG7834 on HAV in liver and feces and how the virus’s ability to cause liver injury is dramatically diminished in mice that had been genetically modified to develop HAV infection and disease.
The pharmaceutical company Hoffmann-La Roche developed RG7834 for use against chronic hepatitis B infections and tested it in humans in a phase 1 trial, but animal studies suggested it may be too toxic for use over long periods of time.
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