On the way for an active agent against hepatitis E

In order to infect an organ, viruses need the help of the host cells. “An effective approach is therefore to identify targets in the host that can be manipulated by drugs so that they no longer perform this helper function,” explains Mara Klöhn.

The researchers became aware of the compound K11777 in a roundabout way: During a control study conducted as part of cell culture studies on the hepatitis C virus with a known active ingredient, they discovered that this active ingredient was also effective against hepatitis E. “However, the drug wasn’t using the same pathway as with the hepatitis C virus, because the hepatitis E virus doesn’t have the target structure that this active substance attacks,” explains Mara Klöhn. This suggested that the drug may have an effect on host cells instead.

The research team narrowed down the possible target structures and turned their attention to cathepsins, which can process proteins, i.e. cleave them. K11777 inhibits many cathepsin types, i.e. blocks their function. Tests in cell culture with human liver cells showed that the compound actually prevents infection with hepatitis E viruses. “In follow-up experiments, we proved our hypothesis that the compound prevents cathepsin L from cleaving and opening up the viral capsid,” says Mara Klöhn. “This means that the virus can no longer infect host cells.”

Hepatitis E

The hepatitis E virus (HEV) is the main cause of acute viral hepatitis. Approximately 70,000 people die from the disease every year. After the first documented epidemic outbreak between 1955 and 1956, more than 50 years passed before researchers began to address the issue in depth. Acute infections usually clear up spontaneously in patients with an intact immune system. In patients with a reduced or suppressed immune system, such as organ transplant recipients or people infected with HIV, HEV can become chronic. HEV also poses a serious threat to pregnant women. There aren’t any vaccines nor specific active substances against the virus.

Journal: Hepatology
DOI: 10.1097/HEP.0000000000000912
Method of Research: Experimental study
Subject of Research: Cells
Article Title: Targeting Cellular Cathepsins Inhibits Hepatitis E Virus Entry
Article Publication Date: 11-May-2024