Discovery of a fused bicyclic derivative of 4-hydroxypyrrolidine and imidazolidinone as a new anti-HCV agent

Virology. 2023 Sep:586:91-104. doi: 10.1016/j.virol.2023.07.012. Epub 2023 Jul 20.


Hepatitis C virus (HCV) infection causes severe liver diseases and remains a major global public health concern. Current direct-acting antiviral (DAA)-based therapies that target viral proteins involving HCV genome replication are effective, however a minority of patients still fail to cure HCV, rendering a window to develop additional antivirals particularly targeting host functions involving in HCV infection. Here, we utilized the HCV infection cell culture system (HCVcc) to screen in-house compounds bearing host-interacting preferred scaffold for the antiviral activity. Compound HXL-10, a novel fused bicyclic derivative of pyrrolidine and imidazolidinone, was identified as a potent anti-HCV agent with a low cytotoxicity and high specificity. Mechanistic studies showed that HXL-10 neither displayed a virucidal effect nor inhibited HCV genomic RNA replication. Instead, HXL-10 might inhibit HCV assembly by targeting host functions. In summary, we developed a novel anti-HCV agent that may potentially offer additive benefits to the current anti-HCV DDA.

Keywords: Antiviral; Fused bicyclic derivative of pyrrolidine and imidazolidinone; Hepatitis C virus (HCV).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • Hepacivirus / genetics
  • Hepatitis C*
  • Hepatitis C, Chronic*
  • Humans
  • Pyrrolidines / pharmacology
  • Virus Replication


  • Antiviral Agents
  • 4-hydroxypyrrolidine
  • Pyrrolidines