Function and therapeutic potential of cathepsin peptidases during Hepatitis E Virus infection (Cat-HEV)

• Applicant: Professor Dr. Eike Steinmann
• Subject Area: Virology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 518559083

The hepatitis E virus (HEV) is a long-neglected RNA virus and the major causative agent of acute viral hepatitis in humans worldwide. A better understanding of the viral life cycle, including the mechanisms of entry into host cells, is needed to identify novel therapeutic targets. Using a novel and robust HEV cell culture system, we recently observed that inhibition of cysteine proteases of the cathepsin family prevents HEV entry into the host cell and ORF2-capsid protein processing. Based on these findings, we aim to further examine the role of cathepsins during the life cycle of HEV and evaluate the therapeutic potential of different cathepsin inhibitors. Elucidating the determinants of HEV entry into permissive cells is instrumental to understand its host and tissue tropism, and will expand our knowledge of HEV virus-host interactions. Furthermore, viral entry represents a well-validated therapeutic target for small-molecule antagonists. Overall, this project aims to provide novel insights into the molecular mechanisms of HEV entry into host cells and may further reveal new pharmacological strategies.

• DFG Programme: Research Grants