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Efficacy of clarithromycin against H5N1 and H7N9 avian influenza a virus infection in cynomolgus monkeys

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  • Efficacy of clarithromycin against H5N1 and H7N9 avian influenza a virus infection in cynomolgus monkeys

    Antiviral Res. 2019 Aug 14:104591. doi: 10.1016/j.antiviral.2019.104591. [Epub ahead of print]
    Efficacy of clarithromycin against H5N1 and H7N9 avian influenza a virus infection in cynomolgus monkeys.

    Arikata M1, Itoh Y2, Shichinohe S3, Nakayama M3, Ishigaki H3, Kinoshita T3, Le MQ4, Kawaoka Y5, Ogasawara K6, Shimizu T1.
    Author information

    1 Department of Otorhinolaryngology, Shiga University of Medical Science, Japan. 2 Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Japan. Electronic address: yasushii@belle.shiga-med.ac.jp. 3 Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Japan. 4 National Institute of Hygiene and Epidemiology, Hanoi, Viet Nam. 5 Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Department of Pathobiological Sciences, University of Wisconsin-Madison, Madison, WI, USA. 6 Division of Pathology and Disease Regulation, Department of Pathology, Shiga University of Medical Science, Japan; Research Center for Animal Life Science, Shiga University of Medical Science, Otsu, Japan.

    Abstract

    Clarithromycin (CAM), a 14-membered ring macrolide, has anti-inflammatory and immunomodulatory actions and antiviral effects in seasonal influenza virus infection. We examined the prophylactic and therapeutic efficacy of CAM against H5N1 highly pathogenic and H7N9 low pathogenic avian influenza virus infections in cynomolgus monkeys. CAM suppressed H5N1 virus-induced severe signs of disease in the treated monkeys and inhibited virus propagation in tracheal samples and the production of inflammatory cytokines in the lungs of monkeys infected with H5N1 and H7N9 viruses. The prophylactic administration of CAM showed more suppressive effects on clinical signs of disease and viral titers than did therapeutic administration. Thus, since administration of CAM alone showed a tendency to ameliorate clinical sings and to reduce levels of inflammatory cytokines, the macrolides are expected to have effects in combination with the other antiviral drugs on the prophylactic and treatment of patients with severe avian influenza virus infection, which should be further investigated.
    Copyright 2019. Published by Elsevier B.V.


    KEYWORDS:

    Avian influenza virus; Clarithromycin; Cynomolgus monkey; H5N1; H7N9

    PMID: 31421167 DOI: 10.1016/j.antiviral.2019.104591
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