title: (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine is a potent inhibitor of feline immunodeficiency virus infection.
abstract: The antiviral efficacy of acyclic nucleoside phosphonates, including 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine [(R)-PMPDAP] against feline immunodeficiency virus (FIV) infection was determined. (R)-PMPDAP showed the highest selectivity index (> 2,000) in vitro. Treatment of experimentally FIV-infected asymptomatic cats with PMEA or (R)-PMPDAP had no effect on the CD4+/CD8+ ratio. However, mean plasma viral RNA concentrations decreased significantly in the (R)-PMPDAP-treated cats. Our data show that, in comparison to PMEA, (R)-PMPDAP is a more potent and less toxic inhibitor of FIV replication both in vitro and in vivo.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, The Netherlands.
authors.forename: T W
authors.initials: TW
authors.lastname: Vahlenkamp
authors.forename: A
authors.initials: A
authors.lastname: De Ronde
authors.forename: J
authors.initials: J
authors.lastname: Balzarini
authors.forename: L
authors.initials: L
authors.lastname: Naesens
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: M J
authors.initials: MJ
authors.lastname: van Eijk
authors.forename: M C
authors.initials: MC
authors.lastname: Horzinek
authors.forename: H F
authors.initials: HF
authors.lastname: Egberink
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000378:metabolism; D016089:Immunodeficiency Virus, Feline; D066298:In Vitro Techniques; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000096:biosynthesis; D013601:T-Lymphocytes / Q000821:virology; D014779:Virus Replication / Q000187:drug effects
chemical_list: C090125:9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine; D000998:Antiviral Agents; D009943:Organophosphorus Compounds; D012367:RNA, Viral; D000225:Adenine