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Appl Biochem Biotechnol ; 180(2): 361-81, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27142273

RESUMO

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 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.


Assuntos
Antivirais/uso terapêutico , Didesoxinucleosídeos/síntese química , Didesoxinucleosídeos/uso terapêutico , Doença de Newcastle/tratamento farmacológico , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Antivirais/química , Antivirais/farmacologia , Galinhas , Didesoxinucleosídeos/química , Didesoxinucleosídeos/farmacologia , Hemaglutinação/efeitos dos fármacos , Concentração Inibidora 50 , Simulação de Acoplamento Molecular , Doença de Newcastle/patologia , Fosforilação/efeitos dos fármacos , Relação Quantitativa Estrutura-Atividade , Proteínas Virais de Fusão/metabolismo
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