A new approach for discovering antivirals against hepatitis B and E viruses aims to identify new drug candidates for these life-threatening diseases. Building on his lab’s expertise in human liver pathogens, Alexander Ploss and his team have pioneered new screening platforms and new methods to evaluate therapeutic candidates.
Infection with hepatitis B virus damages the liver and can cause liver cancer. This chronic infection, which is spread by direct contact with bodily fluids, affects over 250 million people worldwide. The current therapy suppresses infection but is not a cure, as it must be taken for life.
Hepatitis E virus typically causes an acute infection that lasts just a few weeks, but it can cause liver failure in immunocompromised individuals and be life-threatening during pregnancy. Most of the world’s 20 million cases occur in developing countries, and the virus is spreading to developed countries through the consumption of tainted pork. The most common treatment for hepatitis E, ribavirin, cannot be used during pregnancy.
Ploss and his team have developed a new high-throughput screen to identify small molecules capable of interfering with the life cycle of hepatitis B virus, with the goal of providing a cure rather than just a treatment. They’ve developed a sensitive system for rapidly testing molecules using an inactive virus that does not create a biosafety risk.
For hepatitis E virus, Ploss and his team have developed a system for culturing the virus in human liver cells in the lab. They can use these infected cells to identify new strategies to attack the virus, and rapidly screen for small molecules that interfere with the viral life cycle.
Once candidate molecules are identified, the team will evaluate them in a variety of state-of-the-art cell culture systems and animal models available in the Ploss lab, which is one of the few labs in the world to produce mice with livers that are susceptible to human hepatitis viruses.
“Our work has the potential to address important global health care needs and lead to better treatments. It also provides insights into the biology of these viruses and suggests new ways to target them.”
-Alexander Ploss, Associate Professor of Molecular Biology
Team members: Postdoctoral research associates Qiang Ding and Lei Wei; graduate students Ila Nimgaonkar and Benjamin Winer
Collaborator: Hahn Kim, director of the Small Molecule Screening Center at Princeton University
Development status: Patent protection is pending. Princeton is seeking outside interest for further development of this technology.
Funding: New Jersey Health Foundation
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