Research Identifies Potential Treatment Target for Hepatitis B Virus

A recent study from Memorial Sloan Kettering Cancer Center (MSK), Weill Cornell Medicine, and The Rockefeller University has uncovered a potential treatment target for hepatitis B virus (HBV), which infects nearly 5% of the global population and is a leading cause of liver cancer. The research team disrupted the virus’s ability to infect liver cells in the laboratory using an anticancer drug, CBL137, currently in clinical trials.

HBV's ability to cause long-term liver damage and cancer has long been linked to a viral protein called X, which is necessary for the virus to establish infection. However, how this protein is produced, given that the gene encoding it is inside the virus's genome, remained a mystery. The research team found that HBV’s DNA needs to be packaged into nucleosomes, which are the building blocks of chromatin, the material that makes up chromosomes, for the X gene to be transcribed and the virus to replicate. 

“This project started from our fundamental interest in how the virus’s chromosomes might look and function and led to unexpected discoveries of how the viral infection is established in human cells,” explained Yael David, senior author on the paper published in Cell.

By utilizing advanced techniques to study this process, the team discovered that disrupting the formation of these nucleosomes could block the virus’s ability to infect liver cells. Among five tested compounds, CBL137 was the only one to prevent protein X production in liver cells, using very low doses that did not harm human cells.

The next step in the research is to test CBL137 in animal models to evaluate its safety and effectiveness. The discovery could potentially lead to treatments that target chronic HBV infections and provide a new option for those already infected, as current treatments can only suppress the virus but not cure it.