3-drug synergistic interactions of small molecular inhibitors of hepatitis C virus replication.
Small molecular inhibitors of hepatitis C virus (HCV) replication provide remarkable potency, but the rapid selection of resistance mutations will require that these agents be used in combination for clinical treatment. Using a model HCV replicon system, we have extended prior in vitro studies of double combinations of candidate small molecular inhibitors to studies evaluating the simultaneous use of 3 agents. This was done in an effort to anticipate conditions that might ultimately be required clinically. We formally demonstrate synergistic antiviral activity with 3-drug combinations in this model, further supporting the concept of clinical investigations of combination therapy for HCV infection.
Grünberger
Christian
C
Department of Medicine, Division of Infectious Diseases, University of California, San Diego, La Jolla, USA.
Wyles
David L
DL
Kaihara
Kelly A
KA
Schooley
Robert T
RT
D000998:Antiviral Agents / Q000494:pharmacology; D004357:Drug Synergism; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D019384:Nucleic Acid Synthesis Inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D019384:Nucleic Acid Synthesis Inhibitors; D011480:Protease Inhibitors