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(1.2): Antiviral Res. 2008 Jul 1. [Epub ahead of print]
Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N.
Smee DF, Bailey KW, Wong MH, O'Keefe BR, Gustafson KR, Mishin VP, Gubareva LV. - Institute for Antiviral Research, Utah State University, Logan, UT, USA.
Cyanovirin-N (CV-N), a protein derived from Nostoc ellipsosporum, neutralizes influenza virus infectivity by binding to specific high-mannose oligosaccharides (oligomannose-8 and -9) at glycosylation sites on the viral hemagglutinin HA1 subunit.
Mouse-adapted viruses lose sensitivity to CV-N due to HA1 mutations that eliminate these glycosylation sites.
Recently we created a hybrid (reassortant) influenza A/WSN/33 (H1N1) virus containing the HA gene of A/New Caledonia/20/99 (H1N1) with an Asp225Gly mutation in the HA1, that was lethal to mice yet retained sensitivity to CV-N.
We then utilized this model system to test the efficacy of CV-N against influenza.
CV-N efficacy was dose-responsive from 0.0625 to 1mg/kg/day when administered intranasally (i.n.) twice daily for 4 days starting 4h prior to virus exposure.
In a second study, survival benefit was seen with CV-N treatments (0.5mg/kg/day for 4 days) beginning at -4 or +6h, but was significantly reduced at +12h.
The early treatment resulted in up to 100% survival and 1000-fold reduction in lung virus titer on day 3 of the infection.
In contrast, ribavirin (a positive control-75mg/kg/day) treatment resulted in 30% survival and 30-fold decrease in lung virus titers.
Lung consolidation scores and lung weights were significantly reduced by CV-N and ribavirin treatment on day 6 of the infection.
Ferrets infected with a non-animal adapted influenza A/Charlottesville/31/95 (H1N1) virus were treated intranasally with CV-N (50mug twice daily for 5 days starting 24h before virus challenge).
They exhibited 100-fold lower viral titers in nasal washes than placebos 1 day after treatment, but virus titers were equivalent on days 2-7.
CV-N has the potential for prophylaxis and early initiation of treatment of influenza virus infections.
PMID: 18601954 [PubMed - as supplied by publisher]
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Treatment of influenza A (H1N1) virus infections in mice and ferrets with cyanovirin-N.
Smee DF, Bailey KW, Wong MH, O'Keefe BR, Gustafson KR, Mishin VP, Gubareva LV. - Institute for Antiviral Research, Utah State University, Logan, UT, USA.
Cyanovirin-N (CV-N), a protein derived from Nostoc ellipsosporum, neutralizes influenza virus infectivity by binding to specific high-mannose oligosaccharides (oligomannose-8 and -9) at glycosylation sites on the viral hemagglutinin HA1 subunit.
Mouse-adapted viruses lose sensitivity to CV-N due to HA1 mutations that eliminate these glycosylation sites.
Recently we created a hybrid (reassortant) influenza A/WSN/33 (H1N1) virus containing the HA gene of A/New Caledonia/20/99 (H1N1) with an Asp225Gly mutation in the HA1, that was lethal to mice yet retained sensitivity to CV-N.
We then utilized this model system to test the efficacy of CV-N against influenza.
CV-N efficacy was dose-responsive from 0.0625 to 1mg/kg/day when administered intranasally (i.n.) twice daily for 4 days starting 4h prior to virus exposure.
In a second study, survival benefit was seen with CV-N treatments (0.5mg/kg/day for 4 days) beginning at -4 or +6h, but was significantly reduced at +12h.
The early treatment resulted in up to 100% survival and 1000-fold reduction in lung virus titer on day 3 of the infection.
In contrast, ribavirin (a positive control-75mg/kg/day) treatment resulted in 30% survival and 30-fold decrease in lung virus titers.
Lung consolidation scores and lung weights were significantly reduced by CV-N and ribavirin treatment on day 6 of the infection.
Ferrets infected with a non-animal adapted influenza A/Charlottesville/31/95 (H1N1) virus were treated intranasally with CV-N (50mug twice daily for 5 days starting 24h before virus challenge).
They exhibited 100-fold lower viral titers in nasal washes than placebos 1 day after treatment, but virus titers were equivalent on days 2-7.
CV-N has the potential for prophylaxis and early initiation of treatment of influenza virus infections.
PMID: 18601954 [PubMed - as supplied by publisher]
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