RFI-641, a potent respiratory syncytial virus inhibitor.
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.
Huntley
Clayton C
CC
Department of Infectious Disease and Chemical Sciences, Wyeth-Ayerst Research, Pearl River, New York 10965, USA. huntlec@war.wyeth.com
Weiss
William J
WJ
Gazumyan
Anna
A
Buklan
Aron
A
Feld
Boris
B
Hu
William
W
Jones
Thomas R
TR
Murphy
Timothy
T
Nikitenko
Antonia A
AA
O'Hara
Bryan
B
Prince
Gregory
G
Quartuccio
Susan
S
Raifeld
Yuri E
YE
Wyde
Philip
P
O'Connell
John F
JF
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
D000998:Antiviral Agents; C434804:RFI 641; D013449:Sulfonamides; D014227:Triazines