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Arch Med Res. 2015 Jan;46(1):8-16. doi: 10.1016/j.arcmed.2014.12.002. Epub 2014 Dec 15.

In vitro evaluation of synergistic inhibitory effects of neuraminidase inhibitors and methylglyoxal against influenza virus infection.

Author information

1
Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
2
Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; Central Research Center, AVSS Corporation, Nagasaki, Japan.
3
Laboratory of Molecular Biology of Infectious Agents, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan; Central Research Center, AVSS Corporation, Nagasaki, Japan. Electronic address: nobnob@nagasaki-u.ac.jp.

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.

KEYWORDS:

Anti-influenza viral drug; Influenza virus; Manuka honey; Methylglyoxal; Neuraminidase inhibitors; Synergistic effect

PMID:
25523147
DOI:
10.1016/j.arcmed.2014.12.002
[Indexed for MEDLINE]

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