title: RFI-641, a potent respiratory syncytial virus inhibitor.
abstract: Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of acute upper and lower respiratory tract infections in infants, young children, and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo activity. RFI-641 is active against both RSV type A and B strains. The viral specificity and the large therapeutic window of RFI-641 (>100-fold) indicate that the antiviral activity of the compound is not due to adverse effects on normal cells. The potent in vitro activity of RFI-641 can be translated to efficacy in vivo: RFI-641 is efficacious when administered prophylactically by the intranasal route in mice, cotton rats, and African green monkeys. RFI-641 is also efficacious when administered therapeutically (24 h postinfection) in the monkey model. Mechanism of action studies indicate that RFI-641 blocks viral F protein-mediated fusion and cell syncytium formation.
authors.affiliation: Department of Infectious Disease and Chemical Sciences, Wyeth-Ayerst Research, Pearl River, New York 10965, USA. huntlec@war.wyeth.com
authors.forename: Clayton C
authors.initials: CC
authors.lastname: Huntley
authors.forename: William J
authors.initials: WJ
authors.lastname: Weiss
authors.forename: Anna
authors.initials: A
authors.lastname: Gazumyan
authors.forename: Aron
authors.initials: A
authors.lastname: Buklan
authors.forename: Boris
authors.initials: B
authors.lastname: Feld
authors.forename: William
authors.initials: W
authors.lastname: Hu
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Jones
authors.forename: Timothy
authors.initials: T
authors.lastname: Murphy
authors.forename: Antonia A
authors.initials: AA
authors.lastname: Nikitenko
authors.forename: Bryan
authors.initials: B
authors.lastname: O'Hara
authors.forename: Gregory
authors.initials: G
authors.lastname: Prince
authors.forename: Susan
authors.initials: S
authors.lastname: Quartuccio
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Raifeld
authors.forename: Philip
authors.initials: P
authors.lastname: Wyde
authors.forename: John F
authors.initials: JF
authors.lastname: O'Connell
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003587:Cytomegalovirus / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy / Q000517:prevention & control / Q000821:virology; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects*; D016205:Sigmodontinae; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D013696:Temperature; D014227:Triazines / Q000494:pharmacology* / Q000627:therapeutic use; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; C434804:RFI 641; D013449:Sulfonamides; D014227:Triazines