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07.05.2018 | Original Article

Triple combination of FDA-approved drugs including flufenamic acid, clarithromycin and zanamivir improves survival of severe influenza in mice

verfasst von: Andrew C. Y. Lee, Kelvin K. W. To, Anna J. X. Zhang, Houshun Zhu, Can Li, Ricky R. Zhang, Ivan F. N. Hung, Richard Y. T. Kao, Kwok-Hung Chan, Kwok-Yung Yuen

Erschienen in: Archives of Virology | Ausgabe 9/2018

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Abstract

Seasonal influenza virus remains a common cause of mortality despite the use of neuraminidase inhibitors. This study evaluated the efficacy of a triple combination of zanamivir, clarithromycin and flufenamic acid (FFA) in the treatment of influenza virus A(H1N1) infection. An in vitro cell protection assay and a multiple-cycle growth assay showed that the antiviral activity of zanamivir was enhanced when combined with clarithromycin or FFA. A mouse challenge model was used here for the evaluation of the in vivo efficacy of the triple combination treatment. We found that mice receiving the triple combination of FFA, zanamivir, and clarithromycin had a significantly better survival rate than those receiving the double combination of zanamivir and clarithromycin (88% versus 44%, P = 0.0083) or zanamivir monotherapy (88% versus 26%, P = 0.0002). Mice in the FFA-zanamivir-clarithromycin triple combination group also exhibited significantly less body weight loss than those in the zanamivir-clarithromycin double combination group. There was no significant difference in the lung viral titers among the different groups from day 2 to day 6 postinfection. However, the levels of IL-1β, TNF-α and RANTES in the FFA-zanamivir-clarithromycin triple combination group were significantly lower than those in the zanamivir-clarithromycin double combination group, zanamivir monotherapy group, or solvent group on day 2 postinfection. Our findings showed that the FFA-zanamivir-clarithromycin triple combination improved the inflammatory markers and survival of severe influenza A(H1N1) infection in mice.

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Titel: Triple combination of FDA-approved drugs including flufenamic acid, clarithromycin and zanamivir improves survival of severe influenza in mice
verfasst von: Andrew C. Y. Lee
Kelvin K. W. To
Anna J. X. Zhang
Houshun Zhu
Can Li
Ricky R. Zhang
Ivan F. N. Hung
Richard Y. T. Kao
Kwok-Hung Chan
Kwok-Yung Yuen
Publikationsdatum: 07.05.2018
Verlag: Springer Vienna
Erschienen in: Archives of Virology / Ausgabe 9/2018
Print ISSN: 0304-8608
Elektronische ISSN: 1432-8798
DOI: https://doi.org/10.1007/s00705-018-3852-4

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Triple combination of FDA-approved drugs including flufenamic acid, clarithromycin and zanamivir improves survival of severe influenza in mice

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