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Design, Synthesis and Biological Evaluation of Novel Phosphorylated Abacavir Derivatives as Antiviral Agents Against Newcastle Disease Virus Infection in Chicken

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Abstract

Newcastle disease virus is the most devastating virus in poultry industry. It can eradicate the entire poultry flocks once infected. This study is aimed to investigate the antiviral efficacy of novel phosphorylated analogues of the drug abacavir (ABC) against Newcastle disease virus (NDV). About 16 analogues of ABC were designed and docking was performed against fusion protein of NDV. Three compounds were identified and selected for synthesis and biological evaluation based on binding affinity and docking scores. The compounds were synthesized and characterized by IR, 1H, 13C, 31P and CHN analysis and mass spectra. These compounds were tested for antiviral efficacy against NDV-infected DF-1 cells. Compound ABC-1 had shown potent antiviral activity as evidenced by significant reduction in plaque units and cytopathic effect. Therefore, ABC-1 was selected to test for NDV-infected chicken survival rate. Effective dose50 concentrations were determined for ABC-1. Antioxidant enzyme levels in brain, liver and lung tissues were estimated. Superoxide dismutase and catalase were significantly raised and lipid peroxidation and HA titer levels were decreased upon treatment with 2 mg/kg body weight ABC-1. Histopathological modifications were also restored in the ABC-1-treated group. These findings demonstrated ABC-1 as a potential antiviral agent against NDV in chicken.

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Acknowledgments

Dr. Lokanatha Valluru is highly thankful to SERB (No. SR/SO/AS-021/2013 dt.29.11.2013), New Delhi, for providing financial assistance in the form of research grant. We are also thankful to Palamur Bioscience, Mahaboobnagar, for providing the cell culture facility and Dr. D. Raniprameela, S.V. Veterinary University, Tirupati, for providing the NDV inoculum.

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Authors and Affiliations

  1. Department of Biotechnology, Dravidian University, Kuppam, 517426, India

    Suresh K. A., Kadiam C. Venkata Subbaiah, Rayapu Lavanya & Lokanatha Valluru

  2. Department of Chemistry, Sri Venkateswara University, Tirupati, 517502, India

    Kuruva Chandrasekhar & Naga Raju Chamarti

  3. Centre for Bioinformatics, Pondicherry University, Pondicherry, 605014, India

    M. Suresh Kumar

  4. Department of Zoology, Sri Venkateswara University, Tirupati, 517502, India

    Rajendra Wudayagiri

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  1. Suresh K. A.
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Correspondence to Lokanatha Valluru.

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Spectroscopic data for synthesized compounds IR, NMR (1H, 13C, 31P), mass spectral data and elemental analysis.

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K. A., S., Venkata Subbaiah, K.C., Lavanya, R. et al. Design, Synthesis and Biological Evaluation of Novel Phosphorylated Abacavir Derivatives as Antiviral Agents Against Newcastle Disease Virus Infection in Chicken. Appl Biochem Biotechnol 180, 361–381 (2016). https://doi.org/10.1007/s12010-016-2104-x

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