Efficacy of the novel parainfluenza virus haemagglutinin-neuraminidase inhibitor BCX 2798 in mice - further evaluation.

Abstract

BACKGROUND:

Human parainfluenza virus type 1 (hPIV-1) causes serious respiratory tract infections, especially in children. This study investigated the efficacy of the novel haemagglutinin-neuraminidase (HN) inhibitor BCX 2798 in the prophylaxis of lethal and the treatment of non-lethal parainfluenza virus infection in mice.

METHODS:

In the prophylaxis model, 129x1/SvJ mice were inoculated with a 90% lethal dose of a recombinant Sendai virus, in which the HN gene was replaced with that of hPIV-1 (rSeV[hPIV-1HN]). The mice were intranasally treated either once or for 5 days with 1 or 10 mg/kg/day of BCX 2798, starting 4 h before infection. In the therapeutic model, mice were infected with 100 plaque-forming units of rSeV(hPIV-1HN) per mouse and treated intranasally with 0.1, 1 or 10 mg/kg/day of BCX 2798 for 5 days, starting 24 or 48 h after infection, or for 4 days starting 72 h after infection.

RESULTS:

Similar to multiple dosing, a single intranasal prophylaxis with 1 or 10 mg/kg of BCX 2798 protected approximately 40% or 90%, respectively, of mice from death by rSeV(hPIV-1HN) infection. BCX 2798 also significantly reduced virus lung titres (in a dose- and time-dependent manner) and reduced histopathological changes in the airways of non-lethally infected mice at multiple intranasal dosages in the therapeutic model, with the lowest effective dosage being 0.1 mg/kg/day administered 24 h after infection.

CONCLUSIONS:

BCX 2798 was effective in the prophylaxis of lethal and in the therapy of non-lethal parainfluenza virus infection in mice, suggesting further consideration of BCX 2798 for clinical trials.

• Authors: Irina V Alymova, Makiko Watanabe, Kelli L Boyd, Pooran Chand, Y Sudhakara Babu, Allen Portner
• Journal: Antiviral therapy (Antivir Ther) Vol. 14 Issue 7 Pg. 891-8 ( 2009) ISSN: 1359-6535 [Print] England
• PMID: 19918093 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 4-zido-5-isobutyrylamino-2,3-didehydro-2,3,4,5-tetradeoxyglycerogalacto-2-nonulopyranosic acid
• Azides
• Enzyme Inhibitors
• HN Protein
• Hexuronic Acids

Topics

• Administration, Intranasal
• Animals
• Azides (administration & dosage, metabolism)
• Cell Line
• Dose-Response Relationship, Drug
• Enzyme Inhibitors (administration & dosage, metabolism)
• Female
• HN Protein (metabolism)
• Hexuronic Acids (administration & dosage, metabolism)
• Humans
• Macaca mulatta
• Mice
• Parainfluenza Virus 1, Human (drug effects, metabolism)
• Premedication
• Respirovirus Infections (drug therapy, metabolism, virology)
• Treatment Outcome