title: [Antiviral activity in vitro and pharmacokinetics of HCV entry inhibitor AVR560].
abstract: Several novel compounds were found to be potent inhibitors of the HCV (JFH-1 isolate) infection in vitro. Human serum did not significantly reduce antiviral activity of the lead compound, AVR560 (< 4-fold). The immunohistochemistry studies with the Huh7 cell line, infectable with the HCV (JFH-1 strain), demonstrated that AVR560 inhibited the early steps of viral infection and blocked the spread of the HCV infection in tissue culture. The cytotoxicity in Huh7 and Vero-76 cell lines was mild. AVR560 proved to be a specific HCV inhibitor and exhibited no activity against other flaviviruses such as yellow fever (strain 17D), West Nile (strain NY99), and dengue (New Guinea type 2) in in vitro infection experiments. AVR560 also did not inhibit any of the tested human CYP450 isozymes (3A4, 1A2, 2C19 and 2D6). In the pharmacokinetic studies in mice, rats and dogs, favorable pharmacokinetic profiles and good oral bioavailability were observed for AV560. Further pre-clinical studies with this novel HCV inhibitor are in progress.
authors.forename: A V
authors.initials: AV
authors.lastname: Ivashchenko
authors.forename: P M
authors.initials: PM
authors.lastname: Iamanushkin
authors.forename: O D
authors.initials: OD
authors.lastname: Mit'kin
authors.forename: E V
authors.initials: EV
authors.lastname: Ezhova
authors.forename: O M
authors.initials: OM
authors.lastname: Korzinov
authors.forename: E A
authors.initials: EA
authors.lastname: Bulanova
authors.forename: A G
authors.initials: AG
authors.lastname: Koriakova
authors.forename: P V
authors.initials: PV
authors.lastname: Vyshemirskaia
authors.forename: V V
authors.initials: VV
authors.lastname: Bychko
authors.forename: A A
authors.initials: AA
authors.lastname: Ivashchenko
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003716:Dengue Virus / Q000187:drug effects / Q000254:growth & development; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D016174:Hepacivirus / Q000187:drug effects* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology; D022781:Hepatocytes / Q000187:drug effects / Q000821:virology; D006801:Humans; D051379:Mice; D010879:Piperazines / Q000493:pharmacokinetics / Q000494:pharmacology*; D010880:Piperidines / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D014709:Vero Cells; D053586:Virus Internalization / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects*; D014902:West Nile virus / Q000187:drug effects / Q000254:growth & development; D015005:Yellow fever virus / Q000187:drug effects / Q000254:growth & development
chemical_list: C000600959:AVR-560; D000998:Antiviral Agents; D010879:Piperazines; D010880:Piperidines; D003577:Cytochrome P-450 Enzyme System