Study paves way for active drug against hepatitis E

There is currently no specific active substance against hepatitis E. Since the disease kills 70,000 people every year, researchers are actively searching for a cure. A team from the Department of Molecular and Medical Virology at the Ruhr University Bochum, Germany, may have found what they were looking for.

The researchers showed that the compound K11777 prevents the virus from exiting its shell by cleaving the viral capsid in host cells. This means that the virus can no longer infect cells. "The compound is already being tested in clinical trials against other viruses, such as SARS-CoV-2," says lead author Mara Klöhn. "We still have a lot of work to do to see if it can be used as an active agent against hepatitis E, but this is a first step."

The researchers published their findings in the journal Hepatology.

Help from the host cell

Viruses need help from host cells to infect an organ. “An effective approach is to identify targets in the host that can be manipulated by drugs so that they no longer perform this auxiliary function,” explains Klehn.

The researchers learned about the compound K11777 in a roundabout way: during a control study conducted as part of cell culture studies of the hepatitis C virus with a known active ingredient, they found that this active ingredient was also effective against hepatitis E.

“However, the drug did not use the same pathway as with the hepatitis C virus, because the hepatitis E virus does not have a target structure that this active substance targets,” explains Klehn. This suggested that the drug could act on the host cells.

The team narrowed down the possible target structures and turned their attention to cathepsins, which can process proteins, i.e. Break them down. K11777 inhibits many types of cathepsins, i.e. Blocks their function. Cell culture tests with human liver cells showed that the compound does indeed prevent infection with hepatitis E viruses.

"In subsequent experiments, we proved our hypothesis that the compound prevents cathepsin L from cleaving and opening the viral capsid," says Klehn. "This means that the virus can no longer infect host cells."

Hepatitis E

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis. Approximately 70,000 people die from the disease each year. More than 50 years passed after the first documented epidemic outbreak in 1955-1956 before researchers began to study the problem in depth.

Acute infections usually resolve on their own in patients with normal immune systems. In patients with weakened or suppressed immune systems, such as organ transplant recipients or people infected with HIV, HEV can become chronic. HEV also poses a serious threat to pregnant women. There are currently no vaccines or specific active substances against the virus.