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Flavocoxid exerts a potent antiviral effect against hepatitis B virus

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Abstract

Introduction

Flavocoxid is a proprietary blend of two flavonoids, baicalin and catechin, and recent evidence has shown that bioflavonoids may exert antiviral activities. The potential antiviral activity of Flavocoxid against hepatitis B virus (HBV) was evaluated. Additionally, it was investigated if Flavocoxid used in combination with Entecavir could potentiate its anti-HBV activity.

Materials and methods

Hepatoma cells replicating HBV were treated with Flavocoxid, or Entecavir alone or in combination for up to 5 days. Viral replicative intermediates, transcripts, and cccDNA levels were evaluated in HBV-replicating cells by real-time PCR, Southern and Northern blotting. Expression profiling was performed using TaqMan low-density arrays.

Results

Flavocoxid treatment induced a reduction of HBV replicative intermediates, the amount of transcripts, and HBsAg levels. Flavocoxid and Entecavir combination therapy further decreased the amount of HBV replicative intermediates, compared to Flavocoxid alone. Importantly, Flavocoxid alone or in combination with Entecavir also induced a reduction of cccDNA. Gene-expression analysis showed that Flavocoxid activates type I IFNs-signaling and dampens the HBV-induced inflammatory response.

Conclusions

Flavocoxid inhibits HBV replication by targeting multiple steps of viral life cycle. These results indicate that the antiviral activity of Entecavir is potentiated by Flavocoxid, suggesting that this medical food might be considered as an adjuvant for anti-HBV therapy.

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Acknowledgements

Flavocoxid was a kind gift from Primus Pharmaceuticals, Inc (Scottsdale, AZ, USA); Entecavir was kindly provided by Bristol-Myers Squibb. The study has been performed with Departmental funding assigned to Prof. Francesco Squadrito, Prof. Teresa Pollicino, and Prof. Giovanni Raimondo.

Author information

Authors and Affiliations

  1. Division of Clinical and Molecular Hepatology, Department of Human Pathology, University Hospital of Messina, Via Consolare Valeria, 98125, Messina, Italy

    Teresa Pollicino, Cristina Musolino & Giovanni Squadrito

  2. Department of Clinical and Experimental Medicine, Section of Pharmacology, University of Messina, Via Consolare Valeria, Torre Biologica 5th floor, c/o AOU Policlinico G. Martino, Via C. Valeria Gazzi, 98125, Messina, Italy

    Natasha Irrera, Alessandra Bitto, Daniele Lombardo, Martina Timmoneri, Letteria Minutoli, Giovanni Raimondo & Francesco Squadrito

  3. Department of Biomedical and Dental Sciences and Morphological and Functional Sciences, University of Messina, Via Consolare Valeria, 98125, Messina, Italy

    Domenica Altavilla

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  1. Teresa Pollicino
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  2. Cristina Musolino
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  3. Natasha Irrera
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  4. Alessandra Bitto
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  9. Giovanni Squadrito
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  10. Francesco Squadrito
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Correspondence to Teresa Pollicino or Francesco Squadrito.

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The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

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Responsible Editor: Mauro Teixeira.

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Pollicino, T., Musolino, C., Irrera, N. et al. Flavocoxid exerts a potent antiviral effect against hepatitis B virus. Inflamm. Res. 67, 89–103 (2018). https://doi.org/10.1007/s00011-017-1099-2

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  • DOI: https://doi.org/10.1007/s00011-017-1099-2

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