title: Feline immunodeficiency virus plasma load reduction by a retroinverso octapeptide reproducing the Trp-rich motif of the transmembrane glycoprotein.
abstract: The Trp-rich motif (TrpM) of the transmembrane glycoprotein (TM) of lentiviruses is an attractive domain on which to design new potential cell entry peptide inhibitors. We recently demonstrated that an octapeptide reproducing the TrpM of feline immunodeficiency virus (FIV), designated C8, broadly inhibited this virus in vitro and that the retroinverso analogue of this peptide (riC8) was almost as inhibitory and exhibited features suggestive of a much increased stability. Here, we demonstrated that riC8 is indeed highly stable, maintaining its concentration unchanged for at least 24 h in cat serum in vitro. Furthermore, once inoculated into cats, riC8 produced no major acute toxic effects and exhibited satisfactory pharmacokinetic properties. Finally, we report the results of a short-term monotherapy experiment in chronically FIV-infected cats showing that riC8 is well tolerated and also has substantial antiviral activity in vivo. In particular, the mean viral load of riC8-treated animals declined progressively with increasing time of treatment, whereas that of control animals given C8 or solvent alone did not. These results provide the first evidence that clinically useful inhibition of virus replication with a small peptide derived from a functional domain of the TM of a lentivirus can be achieved in vivo.
authors.affiliation: Retrovirus Centre and Virology Section, Department of Experimental Pathology, University of Pisa, Pisa, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Giannecchini
authors.forename: Maria Claudia
authors.initials: MC
authors.lastname: Alcaro
authors.forename: Patrizia
authors.initials: P
authors.lastname: Isola
authors.forename: Olimpia
authors.initials: O
authors.lastname: Sichi
authors.forename: Mauro
authors.initials: M
authors.lastname: Pistello
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Papini
authors.forename: Paolo
authors.initials: P
authors.lastname: Rovero
authors.forename: Mauro
authors.initials: M
authors.lastname: Bendinelli
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002415:Cats; D045744:Cell Line, Tumor; D002908:Chronic Disease; D004353:Drug Evaluation, Preclinical; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology; D005260:Female; D016089:Immunodeficiency Virus, Feline / Q000187:drug effects* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*; D014364:Tryptophan; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; D014364:Tryptophan