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Anti-influenza A virus activity of flavonoids in vitro: a structure–activity relationship

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A Correction to this article was published on 13 December 2022

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Abstract

Secondary plant metabolites from food extracts, namely daidzein, quercetin, and luteolin, exhibit anti-influenza virus effects, with IC50 values of 143.6, 274.8, and 8.0 μM, respectively. The activities of these metabolites differ depending on the functional groups. Therefore, in this study, we focused on members of the flavonoid group, and investigated the anti-influenza viral effects of different flavonoid classes (flavone, isoflavone, flavonol, flavanone, and flavan-3-ol) in vitro. The IC50 values were 4.9–82.8 μM, 143.6 μM, 62.9–477.8 μM, 290.4–881.1 μM, and 22.9–6717.2 μM, respectively, confirming their activity. The modifying group factors (number, position, type) in the flavonoid skeleton may be significantly related to the anti-influenza virus activity. Moreover, time-of-addition assay revealed that the mechanism of inhibition varied for the different classes; for example, flavonoids that inhibit virus adsorption or the early stage of viral growth. Interestingly, all the examined flavonoids inhibited the late stages of viral growth, suggesting that flavonoids mainly inhibit the late events in viral growth before the release of viral particles. Additionally, apigenin might be effective against oseltamivir-resistant strains. Our results may be important in the development of anti-influenza virus therapeutic strategies in the future.

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Fig. 1
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Data availability

All data relevant to the study are included in the manuscript. The data analyzed during the present study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by Grant-in-Aid for Scientific Research (C) (Grant numbers 18K11117 and 22K11792) from the Japan Society for the Promotion of Science (KAKENHI).

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Author notes

  1. Ryosuke Morimoto

    Present address: Faculty of Human Life Science, Shikoku University, Tokushima, 771-1192, Japan

Authors and Affiliations

  1. Department of Food Sciences and Nutrition, School of Food Sciences and Nutrition, Mukogawa Women’s University, Ikebiraki-cho 6-46, Nishinomiya, Hyogo, 663-8558, Japan

    Ryosuke Morimoto, Akari Hanada, Chiaki Matsubara, Yuka Horio & Yuji Isegawa

  2. Toyo Institute of Food Technology, Kawanishi, Hyogo, 666-0026, Japan

    Hidenobu Sumitani

  3. Faculty of Parmaceutical Sciences, Hokuriku University, Kanazawa, Ishikawa, 920-1180, Japan

    Tokutaro Ogata

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Contributions

Material preparation and collection and analyses of data were performed by RM, AH, CM, HS, and YH. New tools and reagents were provided by TO. YI conceived and supervised the study. The first draft of the manuscript was written by RM, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript, which was edited by YI.

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Correspondence to Yuji Isegawa.

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The authors declare no conflict of interest.

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The original online version of this article was revised as the values of IC50 and SI were aligned incorrectly in table 2 and corrected in this version.

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Morimoto, R., Hanada, A., Matsubara, C. et al. Anti-influenza A virus activity of flavonoids in vitro: a structure–activity relationship. J Nat Med 77, 219–227 (2023). https://doi.org/10.1007/s11418-022-01660-z

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