Pre-treatment with Scopolamine Naturally Suppresses Japanese Encephalitis Viral Load in Embryonated Chick Through Regulation of Multiple Signaling Pathways

Applied Biochemistry and Biotechnology (2021)Cite this article

Abstract

Suitable recognition of invasive microorganisms is a crucial factor for evoking a strong immune response that can combat the pathogen. Toll-like receptors (TLRs) play a pivotal role in the induction of this innate immune response through stimulation of interferons (IFNs) that control viral replication in the host via distinct signaling pathways. Though the antiviral property of Atropa belladonna has been established, yet the role of one of its active components scopolamine in modulating various factors of the innate immune branch has not yet been investigated until date. Thus, the present study was conducted to assess the antiviral effects of scopolamine and its immunomodulatory role against Japanese encephalitis virus (JEV) infections in embryonated chick. Pre-treatment with scopolamine hydrobromide showed a significant decrease in the viral loads of chorioallantoic membrane (CAM) and brain tissues. Molecular docking analysis revealed that scopolamine hydrobromide binds to the active site of non-structural protein 5 (NS5) that has enzymatic activities required for replication of JEV, making it a highly promising chemical compound against the virus. The binding contributions of different amino acid residues at or near the active site suggest a potential binding of this compound. Pre-treatment with the scopolamine hydrobromide showed significant upregulation of different TLRs like TLR3, TLR7, and TLR8, interleukins like IL-4, and IL-10, as well as IFNs and their regulatory factors. However, virus-infected tissues (direct infection group) exhibited higher TLR4 expression as compared to scopolamine hydrobromide pre-treated, virus-infected tissues (medicine pre-treated group). These results indicate that scopolamine hydrobromide contributes much to launch antiviral effects by remoulding the TLR and IFN signaling pathways that are involved in sensing and initiating the much-needed anti-JEV responses.

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Data Availability

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Acknowledgements

The authors express their deep gratitude of thanks to the Department of Microbiology, Peerless Hospital & B.K Roy Research Centre, Kolkata, Department of Cardiology, R.G Kar Medical College & Hospital, Kolkata, and Department of Botany, Berhampur University, Odisha. We are also thankful to the National Institute of Virology, Pune, for providing the viral strains of JEV. The authors are also deeply indebted to Rev. Dr. Dominic Savio, S.J., Principal and Rector, St. Xavier’s College (Autonomous), Kolkata, Dr. Subhankar Tripathi, Principal, Sarsuna College, Kolkata, and Dr. Satadal Das, Consultant Senior Microbiologist, Peerless Hospital & B.K Roy Research Centre, for their constant support and guidance throughout.

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Affiliations

  1. Department of Biotechnology, National Institute of Technology Durgapur, Durgapur, West Bengal, India

    Arghyadeep Bhattacharjee

  2. Department of Biotechnology, Regional Centre for Biotechnology, Faridabad, Haryana, India

    Rajarshi Chaudhuri

  3. Department of Botany, Berhampur University, Berhampur, Odisha, India

    Jiban Jyoti Dash

  4. Department of Cardiology, R.G Kar Medical College & Hospital, Kolkata, West Bengal, India

    Manish Saha

  5. Department of Microbiology, Sarsuna College, Kolkata, West Bengal, India

    Lopamudra Choudhury

  6. Post-Graduate Department of Biotechnology, St. Xavier’s College (Autonomous), Kolkata, West Bengal, India

    Souvik Roy

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The experimental design was performed collectively by all the authors. Preparation of reagents and samples along with data collection and analysis was done by AB, LC, and SR. The manuscript was written by AB and RC with inputs from all the authors. Conceptualization: AB, MS; methodology: AB, LC, and JJD; writing—original draft preparation: AB; writing review and editing: AB, RC, and SR; resources: AB, JJD, and MS.

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Bhattacharjee, A., Chaudhuri, R., Dash, J.J. et al. Pre-treatment with Scopolamine Naturally Suppresses Japanese Encephalitis Viral Load in Embryonated Chick Through Regulation of Multiple Signaling Pathways. Appl Biochem Biotechnol (2021). https://doi.org/10.1007/s12010-021-03526-8

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Keywords

  • Toll-like receptors
  • Interferons
  • Japanese encephalitis virus
  • Scopolamine hydrobromide
  • Embryonated chick
  • Signaling pathways