2023-06-21 08:37:05
Ruhr University Bochum on June 21, 2023
There are currently no specific drugs against hepatitis E. Doctors only have access to the broad-spectrum antiviral drug ribavirin, which often causes severe side effects. Drugs against other hepatitis viruses only help to a limited extent. A team from the Computational Virology junior research group led by Dr. Daniel Todt in the Department of Molecular and Medical Virology at the Ruhr University Bochum together with researchers from Berlin, Hamburg and Hanover discovered that a single mutation in the virus means that the treatment is less effective. The researchers report in the journal Hepatology on June 20, 2023.
Which virus variants circulate in the blood?
Daniel Todt, André Gömer, Eike Steinmann (back from left), Michelle Jagst (front left) and Mara Klöhn from the Department of Medical and Molecular Virology at the Ruhr University
© RUB, Marquard
In an earlier clinical study in which the Bochum researchers were involved, patients with chronic hepatitis E virus (HEV) infection were treated with the active substance sofosbuvir, which was actually developed for the treatment of hepatitis C. “In this pilot study, we were able to observe that treatment with sofosbuvir was initially effective,” reports Dr. Andre Gomer. “The amount of viral RNA initially dropped. In the course of the observation period, however, it increased again. So the therapy did not bring the desired success,” adds Mara Klöhn. The researchers analyzed samples from these patients to identify variants that could explain the failure of sofosbuvir therapy. They hoped that this would give them new insights that would benefit future drug developments.
Fivefold loss of potency due to a mutation
In the retrospective analysis, they were able to identify a single mutation in the polymerase – a protein responsible for replication of the hepatitis E virus – called A1343V, which occurred in parallel with the resurgence of viral RNA. Laboratory experiments showed that the active ingredient was five times less effective at clearing the mutant virus than other genetic variants of the virus.
The research team is currently examining whether combination therapy with the standard drug ribavirin can prevent the development of the A1343V mutation and would therefore be a promising therapy option. “For the development of future therapies against hepatitis E, we need to better understand the role of this mutation,” concludes Michelle Jagst.
As part of their VirBio project, which is funded by the Federal Ministry of Education and Research, Todt’s working group is researching, among other things, the evolution of viruses and the interaction between virus and host cell using high-throughput sequencing and computer-aided methods.
Hepatitis E
The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. Around 70,000 people die from the disease every year. After the first documented epidemic outbreak in 1955 to 1956, more than 50 years passed before researchers took up the topic intensively. Acute infections usually heal on their own in patients with an intact immune system. In people with a reduced or suppressed immune system, such as organ transplant recipients or those infected with HIV, HEV can become chronic. HEV is also particularly dangerous for pregnant women.
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