Antiviral Efficacy of a Respiratory Syncytial Virus (RSV) Fusion Inhibitor in a Bovine Model of RSV Infection
| Autor: | Jason W. Chien, Laurel J. Gershwin, Anne Carey, Richard L. Mackman, Eugene J. Eisenberg, Michel Perron, Sandy Lewis, Robert Jordan, Heather A. McEligot, Robert G. Strickley, Mark L Anderson, Nicole E. Behrens, Matt X. Shao, Tomas Cihlar |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Indazoles viruses Cattle Diseases Respiratory Syncytial Virus Bovine Respiratory Syncytial Virus Infections Biology medicine.disease_cause Microbiology Antiviral Agents Virus Cell Line Double-Blind Method Viral entry medicine Animals Humans Pharmacology (medical) Lung Pediatric Pharmacology Host cell membrane Sulfonamides Cell Membrane Respiratory infection Bovine Pneumonia Pharmacology and Pharmaceutical Sciences Viral Load respiratory system medicine.disease Virology Infectious Diseases Respiratory syncytial virus (RSV) Medical Microbiology Bronchiolitis Respiratory Syncytial Virus Human Immunology Pneumonia & Influenza Respiratory Pyrazoles Cattle Respiratory Syncytial Virus Infection Viral load Human |
| Zdroj: | Antimicrobial agents and chemotherapy, vol 59, iss 8 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00487-15 |
| Popis: | Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in infants. Effective treatment for RSV infection is a significant unmet medical need. While new RSV therapeutics are now in development, there are very few animal models that mimic the pathogenesis of human RSV, making it difficult to evaluate new disease interventions. Experimental infection of Holstein calves with bovine RSV (bRSV) causes a severe respiratory infection that is similar to human RSV infection, providing a relevant model for testing novel therapeutic agents. In this model, viral load is readily detected in nasal secretions by quantitative real-time PCR (qRT-PCR), and cumulative symptom scoring together with histopathology evaluations of infected tissue allow for the assessment of disease severity. The bovine RSV model was used to evaluate the antiviral activity of an RSV fusion inhibitor, GS1, which blocks virus entry by inhibiting the fusion of the viral envelope with the host cell membrane. The efficacy of GS1, a close structural analog of GS-5806 that is being developed to treat RSV infection in humans was evaluated in two randomized, blind, placebo-controlled studies in bRSV-infected calves. Intravenous administration of GS1 at 4 mg/kg of body weight/day for 7 days starting 24 h or 72 h postinoculation provided clear therapeutic benefit by reducing the viral load, disease symptom score, respiration rate, and lung pathology associated with bRSV infection. These data support the use of the bovine RSV model for evaluation of experimental therapeutics for treatment of RSV. |
| Databáze: | OpenAIRE |
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