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Inhibitory effect of doxycycline against dengue virus replication in vitro

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Abstract

Doxycycline is an antibiotic derived from tetracycline that possesses antimicrobial and anti-inflammatory activities. Antiviral activity of doxycycline against dengue virus has been reported previously; however, its anti-dengue properties need further investigation. This study was conducted to determine the potential activity of doxycycline against dengue virus replication in vitro. Doxycycline inhibited the dengue virus serine protease (DENV2 NS2B-NS3pro) with an IC50 value of 52.3 ± 6.2 μM at 37 °C (normal human temperature) and 26.7 ± 5.3 μM at 40 °C (high fever temperature). The antiviral activity of doxycycline was first tested at different concentrations against DENV2 using a plaque-formation assay. The virus titter decreased significantly after applying doxycycline at levels lower than its 50 % cytotoxic concentration (CC50, 100 μM), showing concentration-dependent inhibition with a 50 % effective concentration (EC50) of approximately 50 μM. Doxycycline significantly inhibited viral entry and post-infection replication of the four dengue serotypes, with serotype-specific inhibition (high activity against DENV2 and DENV4 compared to DENV1 and DENV3). Collectively, these findings underline the need for further experimental and clinical studies on doxycycline, utilizing its anti-dengue and anti-inflammatory activities to attenuate the clinical symptoms of dengue virus infection.

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Abbreviations

DENV1-4:

Dengue virus serotypes 1, 2, 3 and 4

NS2B:

NS2B cofactor amino acid sequence 49-95 in DENV

NS3pro:

NS3 protease amino acid sequence 1-185 in NS3 protease

NS2B-NS3pro:

NS2B fused to NS3pro via 9 amino acids (G4-T-G4)

AMC:

Fluorogenic peptide substrate (Boc-Gly-Arg-Arg-AMC)

CPE:

Cytopathic effect

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Acknowledgments

This project was funded by the University of Malaya, UMRG grant no. RP002-2012 and ERGS grant no. ER016-2013A.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Molecular Medicine, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Hussin A. Rothan, Mohammadjavad Paydar & Rohana Yusof

  2. Department of Genetics, Faculty of Science, Institute of Biological Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Zulqarnain Mohamed

  3. Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Noorsaadah Abd Rahman

Authors
  1. Hussin A. Rothan
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  2. Zulqarnain Mohamed
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  5. Rohana Yusof
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Correspondence to Hussin A. Rothan.

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Rothan, H.A., Mohamed, Z., Paydar, M. et al. Inhibitory effect of doxycycline against dengue virus replication in vitro . Arch Virol 159, 711–718 (2014). https://doi.org/10.1007/s00705-013-1880-7

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  • DOI: https://doi.org/10.1007/s00705-013-1880-7

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