RFI-641, a Potent Respiratory Syncytial Virus Inhibitor

Author:

Huntley Clayton C.1,Weiss William J.1,Gazumyan Anna1,Buklan Aron1,Feld Boris1,Hu William1,Jones Thomas R.1,Murphy Timothy1,Nikitenko Antonia A.1,O'Hara Bryan1,Prince Gregory2,Quartuccio Susan1,Raifeld Yuri E.1,Wyde Philip3,O'Connell John F.123

Affiliation:

1. Department of Infectious Disease and Chemical Sciences, Wyeth-Ayerst Research, Pearl River, New York

2. Virion Systems, Rockville, Maryland

3. Baylor College of Medicine, Houston, Texas

Abstract

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.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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