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Feb 22 2025
1Hepatitis B virus (HBV), a leading cause of liver disease and cancer, may soon meet its match. Researchers from Memorial Sloan Kettering Cancer Center (MSK), Weill Cornell Medicine, and the Rockefeller University have found that a drug initially developed to fight cancer could also disrupt HBV’s ability to infect human liver cells. The study, published in Cell, details how the chromatin-destabilizing molecule CBL137 blocks HBV infection by interfering with the virus’s DNA organization—an essential step in its replication process.
Globally, over 325 million people are chronically infected with HBV, resulting in nearly one million deaths annually due to liver disease and hepatocellular carcinoma. While vaccines are available, they don’t help those already infected. Current treatments suppress the virus but fail to eliminate it, leaving patients at continued risk for liver damage and cancer.
A New Approach to Target HBV
The breakthrough centers on HBV’s dependence on human DNA-packaging proteins, called histones, to organize its DNA into structures known as nucleosomes. These nucleosomes are essential for producing HBV X protein (HBx)—a viral protein that drives infection and cancer progression.
“This raises a classic chicken-and-egg question,” said Yael David, PhD, the study’s senior author. “How does the virus produce enough X protein to establish infection when the gene for HBx is embedded in its genome?”
The research revealed that CBL137 disrupts this process by preventing the virus’s DNA from forming these crucial nucleosome structures. Without proper nucleosome assembly, HBx cannot be produced, effectively stopping the infection before it starts.
Why CBL137 Stands Out
Originally tested for its anticancer properties, CBL137 showed promising antiviral effects at very low concentrations, significantly lower than doses used in cancer clinical trials. Even more encouraging, it specifically targeted HBV without damaging healthy human liver cells.
“This made us optimistic about developing a treatment that could clear HBV infections with minimal side effects,” said David. “If further studies confirm these results, we might finally have a path to a functional cure for chronic hepatitis B.”
Implications for Global Health
HBV remains a global health challenge, particularly in regions like Africa and Asia, where mother-to-child transmission rates are high, and access to vaccines and treatments is limited. A treatment like CBL137 could transform care, offering new hope to millions living with chronic HBV.
Moreover, the findings suggest that CBL137 could have broader applications. The molecule might be effective against other DNA viruses, such as herpesviruses and papillomaviruses, and even show potential for treating HIV-1 infections and human African trypanosomiasis, according to recent studies.
What Comes Next?
While the results are promising, the next step involves testing CBL137 in animal models to evaluate its safety and effectiveness. HBV’s limited host range poses challenges for these trials, but researchers are hopeful.
“This study wouldn’t have been possible without the collaboration between our institutions,” said Nicholas Prescott, PhD, the paper’s first author. “It shows how basic science—driven by curiosity about fundamental biological processes—can lead to discoveries with significant medical potential.”
