In Vitro Evaluation of Synergistic Inhibitory Effects of Neuraminidase Inhibitors and Methylglyoxal Against Influenza Virus Infection

Siriwan Charyasriwong, Ken Watanabe, Ratika Rahmasari, Ayaka Matsunaga, Takahiro Haruyama, Nobuyuki Kobayashi

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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 ~1/100th 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.

Original languageEnglish
Pages (from-to)8-16
Number of pages9
JournalArchives of Medical Research
Volume46
Issue number1
DOIs
Publication statusPublished - 2015

Keywords

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

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