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  • Title: In vitro evaluation of synergistic inhibitory effects of neuraminidase inhibitors and methylglyoxal against influenza virus infection.
    Author: Charyasriwong S, Watanabe K, Rahmasari R, Matsunaga A, Haruyama T, Kobayashi N.
    Journal: Arch Med Res; 2015 Jan; 46(1):8-16. PubMed ID: 25523147.
    Abstract:
    BACKGROUND AND AIMS: Influenza virus infections are serious public health concerns worldwide that cause considerable mortality and morbidity. Moreover, the emergence of resistance to anti-influenza viral agents underscores the need to develop new anti-influenza viral agents and novel treatment strategies. Recently, we identified anti-influenza viral activity of manuka honey. Therefore, we hypothesized that methylglyoxal (MGO), a key component of manuka honey, may impart anti-influenza viral activity. The aim of this study was to evaluate the anti-influenza viral activity of MGO and its potential in combination treatments with neuraminidase (NA) inhibitors. METHODS: MDCK cells were used to evaluate anti-influenza viral activity. To evaluate the mechanism of MGO, plaque inhibition assays were performed. The synergistic effects of MGO and viral NA inhibitors were tested. RESULTS: MGO inhibited influenza virus A/WSN/33 replication 50% inhibitory concentration = 240 ± 190 μM; 50% cytotoxic concentration = 1.4 ± 0.4 mM; selective index (SI) = 5.8, which is related to its virucidal effects. Moreover, we found that MGO showed promising activity against various influenza strains. A synergistic effect was observed by a marked increase in SI of NA inhibitors at ∼1/100(th) of their single usage. A synergistic effect of MGO and oseltamivir was also observed against oseltamivir-resistant virus. CONCLUSIONS: Our results showed that MGO has potent inhibitory activity against influenza viruses and also enhanced the effect of NA inhibitors. Thus, the co-administration of MGO and NA inhibitors should be considered for treatment of influenza virus infections.
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