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

• Published in: Applied biochemistry and biotechnology 2016-09, Vol.180 (2), p.361-381
• Main Authors: K. A., Suresh, Venkata Subbaiah, Kadiam C., Lavanya, Rayapu, Chandrasekhar, Kuruva, Chamarti, Naga Raju, Kumar, M. Suresh, Wudayagiri, Rajendra, Valluru, Lokanatha
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Antiviral agents; Antiviral Agents - chemistry; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Biochemistry; Biotechnology; Body weight; Chemistry; Chemistry and Materials Science; Chickens; Dideoxynucleosides - chemical synthesis; Dideoxynucleosides - chemistry; Dideoxynucleosides - pharmacology; Dideoxynucleosides - therapeutic use; Hemagglutination - drug effects; Inhibitory Concentration 50; Mass spectra; Molecular Docking Simulation; Newcastle disease; Newcastle Disease - drug therapy; Newcastle Disease - pathology; Newcastle Disease - virology; Newcastle disease virus; Newcastle disease virus - drug effects; Paramyxoviridae; Peroxidation; Phosphorylation; Phosphorylation - drug effects; Poultry; Protein synthesis; Quantitative Structure-Activity Relationship; Survival; Viral Fusion Proteins - metabolism; Viral infections
• ISSN: 0273-2289; 1559-0291
• DOI: 10.1007/s12010-016-2104-x

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, 1 H, 13 C, 31 P 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 dose 50 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.