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Development of Hemagglutinin–Neuraminidase Homologous Peptides as Novel Promising Therapeutic Agents Against Peste des Petits Ruminants Virus

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Abstract

The lack of specific antiviral therapy and complications associated with the existing peste des petits ruminants (PPR) vaccines accentuates the search of novel antiviral blocking agents in order to curtail the PPR infection at initial level. The synthetic hemagglutinin–neuraminidase (HN) homologous peptides may compete with the natural HN protein of PPR virus for binding to signaling lymphocytic activation molecule (SLAM) receptor, consequently, may disrupt peste des petits ruminants virus (PPRV) at entry level. Therefore, insilico analysis, synthesis, purification and subsequent characterization of HN homologous peptides were conducted in this study. The HN homologous peptides were synthesized by means of solid phase chemistry and were purified by reversed-phase-high performance liquid chromatography. The mass as well as sequence of HN homologous peptides were assessed by mass spectroscopy while its secondary structure was elucidated by circular dichroism spectroscopy. The binding (interaction) efficacy of HN homologous peptides with PPRV antibodies was assessed via indirect enzyme linked immunosorbent assay, visual detection test (red wine to purple), bathochromic shift under UV–Vis spectrophotometry and lateral flow immunochromatographic strip test. The antiviral properties and cytotoxicity of these peptides were also assessed in B95a cell line with changes in cytopathic effect and titer of PPRV (Sungri/96). The presence of green fluorescein isothiocyanate over the B95a cell surface pointed towards the binding of HN homologous peptides with surface SLAM receptor. Moreover, the intact beta sheet configuration in water and lower cytotoxicity [cytotoxic concentration 50 (CC50) > 1000 µg/ml] of these peptides signifies its in vivo use. Among HN homologous peptides, the binding efficacy and antiviral properties of pep A was relatively high in comparison to pep B and Pep ppr peptides. The prerequisite concentration of HN homologous peptides (pep A = 12.5 µg/ml; pep B = 25 µg/ml; pep ppr = 25 µg/ml) to exemplify its antiviral effect was much lower than its CC50 level. Hence, this study signifies the therapeutic potential of synthetic HN homologous peptides.

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The original contributions presented in the study are included in the article/supplementary materials, further inquiries can be directed to the corresponding author/s.

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Acknowledgements

The authors are thankful to the Director ICAR-IVRI for providing the necessary facilities for carrying out this research work.

Funding

This work was not supported by any public agency or grants.

Author information

Authors and Affiliations

  1. Division of Animal Biochemistry, IVRI, Izatnagar, Bareilly, U.P., 243122, India

    Aditya Agrawal, Anil Gattani, Mahvash Hira Khan & Praveen Singh

  2. Department of Veterinary Physiology and Biochemistry, College of Veterinary Science and Animal husbandry, NDVSU, Rewa, Jabalpur, 486001, India

    Aditya Agrawal

  3. Department of Veterinary Microbiology, BHU, Mirzapur, U.P., 231001, India

    Rajat Varshney

  4. Division of Bacteriology and Mycology, IVRI, Izatnagar, Bareilly, U.P., 243122, India

    Rajat Varshney & R. P. Singh

  5. Department of Veterinary Medicine, College of Veterinary Science and Animal husbandry, NDVSU, Jabalpur, 486001, India

    Rohini Gupta

  6. Division of Veterinary Biotechnology, IVRI, Izatnagar, Bareilly, U.P., 243122, India

    Khushal Singh Solanki

  7. Department of Veterinary Pathology, College of Veterinary Science and Animal husbandry, NDVSU, Rewa, Jabalpur, 486001, India

    Shailesh Kumar Patel

  8. Department of Veterinary Physiology and Biochemistry, College of Veterinary Science and Animal husbandry, NDVSU, Jabalpur, 486001, India

    Anil Gattani & Mahvash Hira Khan

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  1. Aditya Agrawal
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  9. Praveen Singh
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Contributions

AA: Conceptualization, data curation, formal analysis, investigation, methodology, writing—review and editing. RV: Data curation, formal analysis, investigation, methodology, writing—original draft. AG, MHK, RG, KSS and SKP: Formal analysis, methodology. RPS: Supervision, validation, visualization. PS: Conceptualization, data curation, funding acquisition, investigation, project administration, resources, supervision, validation, writing—review and editing. All authors reviewed the manuscript.

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Correspondence to Aditya Agrawal.

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Agrawal, A., Varshney, R., Gattani, A. et al. Development of Hemagglutinin–Neuraminidase Homologous Peptides as Novel Promising Therapeutic Agents Against Peste des Petits Ruminants Virus. Protein J 42, 685–697 (2023). https://doi.org/10.1007/s10930-023-10134-4

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