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Antimicrobial Agents and Chemotherapy, March 2002, p. 841-847, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.841-847.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

RFI-641, a Potent Respiratory Syncytial Virus Inhibitor

Clayton C. Huntley,1* William J. Weiss,1 Anna Gazumyan,1 Aron Buklan,1 Boris Feld,1 William Hu,1 Thomas R. Jones,1 Timothy Murphy,1 Antonia A. Nikitenko,1 Bryan O'Hara,1 Gregory Prince,2 Susan Quartuccio,1 Yuri E. Raifeld,1 Philip Wyde,3 and John F. O'Connell1,2,3

Department of Infectious Disease and Chemical Sciences, Wyeth-Ayerst Research, Pearl River, New York,1 Virion Systems, Rockville, Maryland,2 Baylor College of Medicine, Houston, Texas3

Received 25 June 2001/ Returned for modification 10 September 2001/ Accepted 16 November 2001

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.

* Corresponding author. Mailing address: Wyeth-Ayerst Research, 401 N. Middletown Rd., Bldg. 205, Rm. 216, Pearl River, NY 10965. Phone: (845) 732-5086. Fax: (845) 732-2480. E-mail: huntlec{at}war.wyeth.com.

Antimicrobial Agents and Chemotherapy, March 2002, p. 841-847, Vol. 46, No. 3
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.3.841-847.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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