Researchers have discovered a compound that prevents hepatitis E viruses from replicating.
Photo Credit: © RUB, Marquard
Scientific Frontline: Extended "At a Glance" Summary: Bemnifosbuvir as a Treatment for Hepatitis E
The Core Concept: Bemnifosbuvir is a synthetic nucleotide/nucleoside analogue, currently in clinical trials for hepatitis C, that has been identified as a highly effective inhibitor of the hepatitis E virus (HEV).
Key Distinction/Mechanism: The drug functions by providing "false building blocks" that mimic the natural structural components of viral genetic material. When the hepatitis E virus attempts to copy its genome, it incorporates these synthetic molecules, which successfully halts viral replication while leaving healthy host cells unharmed.
Major Frameworks/Components:
- Nucleotide/Nucleoside Analogues: The foundational pharmacological framework utilizing synthetic molecules structured similarly to DNA/RNA components to disrupt viral synthesis.
- Fluorescent Reporter Virus Screening: An in vitro screening methodology utilizing a modified virus carrying a fluorescent molecule, allowing researchers to visually monitor and quantify viral replication and its active inhibition.
- Preclinical Validation: The methodological progression from cellular assays to animal models to confirm both the compound's safety profile and its direct efficacy against HEV-induced liver inflammation.
Branch of Science: Virology, Pharmacology, Infectious Diseases, and Molecular Biology.
Future Application: If ongoing clinical trials for its use against hepatitis C are successful, bemnifosbuvir could be rapidly deployed as an off-label treatment for hepatitis E infections, providing a specialized therapeutic route where none currently exists.
Why It Matters: Hepatitis E is the leading global cause of acute viral hepatitis, resulting in approximately 70,000 deaths annually. Because there is currently no approved vaccine or specific antiviral medication for HEV, this discovery offers a critical, life-saving therapeutic option, particularly for highly vulnerable populations such as pregnant women, organ transplant recipients, and immunocompromised patients.
A drug that is already in clinical trials against hepatitis C virus can also prevent hepatitis E virus from replicating.
Around 70,000 people die each year from infections with the hepatitis E virus. There is currently neither a vaccine nor a specific drug against this virus. This could change with the identification of bemnifosbuvir as a compound effective against hepatitis E viruses (HEV). An international research team from Bochum, Germany, Heidelberg, Germany, and Beijing, China, has filtered this so-called nucleotide/nucleoside analogue out of a library of such active substances. Since the drug is also effective against the hepatitis C virus and is already in clinical trials for this indication, the researchers hope that it could also become available as a treatment option against the hepatitis E virus in the foreseeable future. They report their findings in the journal “Gut”.
Cooperation partners
The study involved the Department of Molecular and Medical Virology at Ruhr University Bochum, the Dao Thi Lab at the Center for Integrative Infectious Disease Research (CIID) of Heidelberg University Hospital, and the Lin Wang Lab at Peking University in China.
Providing viruses with false building blocks
The starting point in the search for an active substance against HEV was a commercially available library of nucleotide/nucleoside analogues. “These synthetically produced molecules are constructed similarly to the building blocks of our genetic material and likewise to that of viruses,” explains Dr. Mara Klöhn from Ruhr University Bochum.
To find out whether any of the roughly 500 compounds in the library could inhibit HEV replication, the researchers used a new reporter virus that contained a fluorescent molecule. They infected cell cultures with hepatitis E viruses that carried this reporter gene and then added the various candidate compounds. Using fluorescence, they were able to determine whether the virus had continued to replicate or not. “With bemnifosbuvir we were able to see that the virus no longer replicated, while the treated cells remained healthy,” reports Jungen Hu from Heidelberg University. In animal experiments, the Chinese researchers were able to confirm the efficacy of the substance against HEV and liver inflammation. “If the ongoing clinical trials of bemnifosbuvir against hepatitis C are successful, the drug could soon also be available for off-label use against hepatitis E,” says Dr. Viet Loan Dao Thi and Professor Eike Steinmann.
Hepatitis E
The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. Around 70,000 people die from the disease each year. After the first documented epidemic outbreak from 1955 to 1956, it took more than 50 years before researchers began to study the topic intensively. Acute infections usually resolve spontaneously in patients with an intact immune system. In people with a reduced or suppressed immune system, such as organ transplant recipients or individuals with HIV, HEV can become chronic. HEV is also particularly dangerous for pregnant women. There are no vaccine and no specific drug.
Funding: The work was supported by funding from the National Key Research and Development Program of China (2023YFC2306900), the research program “Antiviral Therapies” of the Baden‑Württemberg Stiftung, the German Research Foundation within Collaborative Research Center 1129 (project number 240245660), the German Center for Infection Research – TTU Hepatitis Project 05.823, the Beijing Municipal Natural Science Foundation (L244032), and the National Natural Science Foundation of China (82522053).
Published in journal: Gut
Title: Nucleotide analogue bemnifosbuvir inhibits hepatitis E virus replication in preclinical models
Authors: Jungen Hu, Tianxu Liu, Mara Klöhn, Andrew Freistaedter, Elif Toprak, Huanting Chi, André Gömer, Lilli Pottkaemper, Paula Jordan, Xinyue Yang, He Zhang, Johanna Becker, Shirin Nkongolo, Volker Lohmann, Eike Steinmann, Lin Wang, Viet Loan Dao Thi1
Source/Credit: Ruhr University Bochum
Reference Number: vi032026_01
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