CommentaryWhat are the pros and cons of the use of host-targeted agents against hepatitis C?

•Host-targeted agents block hepatitis C virus production by interacting with host cell components.•Blocking the interaction of a cell component involved in the HCV lifecycle results in blockade of viral production.•Cyclophilin A inhibitors and antagonists of microRNA-122 have reached clinical development.•Host-targeted agents represent ideal “backbones” for pangenotypic drug combinations.•Research on host-targeted approaches to combat viral infections other than HCV should be encouraged.

Hepatitis C virus (HCV) therapy is living a revolution. Host-targeted agents (HTAs) block HCV production by interacting with host cell components. Because they target conserved host proteins, not variable viral proteins, HTAs have the potential for pangenotypic antiviral activity and a high barrier to resistance. Only two HTAs have reached clinical development, including specific inhibitors of cyclophilin A peptidyl-prolyl cis/trans isomerase activity and antagonists of microRNA-122. Cyclophilin inhibitors have proven to be relatively well tolerated and can be confidently used as backbones of all-oral, interferon-free regimens. In addition, HTAs such as cyclophilin inhibitors offer opportunities for “panviral” approaches when they target mechanisms common to viruses of the same or different families. This article forms part of a symposium in Antiviral Research on “Hepatitis C: next steps toward global eradication.”