title: Design, Synthesis and Biological Evaluation of Novel Phosphorylated Abacavir Derivatives as Antiviral Agents Against Newcastle Disease Virus Infection in Chicken.
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, (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.
authors.affiliation: Department of Biotechnology, Dravidian University, Kuppam, 517426, India.
authors.forename: Suresh
authors.initials: S
authors.lastname: K A
authors.affiliation: Department of Biotechnology, Dravidian University, Kuppam, 517426, India.
authors.forename: Kadiam C
authors.initials: KC
authors.lastname: Venkata Subbaiah
authors.affiliation: Department of Biotechnology, Dravidian University, Kuppam, 517426, India.
authors.forename: Rayapu
authors.initials: R
authors.lastname: Lavanya
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati, 517502, India.
authors.forename: Kuruva
authors.initials: K
authors.lastname: Chandrasekhar
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati, 517502, India.
authors.forename: Naga Raju
authors.initials: NR
authors.lastname: Chamarti
authors.affiliation: Centre for Bioinformatics, Pondicherry University, Pondicherry, 605014, India.
authors.forename: M Suresh
authors.initials: MS
authors.lastname: Kumar
authors.affiliation: Department of Zoology, Sri Venkateswara University, Tirupati, 517502, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Wudayagiri
authors.affiliation: Department of Biotechnology, Dravidian University, Kuppam, 517426, India. lokanath.valluru@gmail.com.
authors.forename: Lokanatha
authors.initials: L
authors.lastname: Valluru
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002645:Chickens; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006384:Hemagglutination / Q000187:drug effects; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D009521:Newcastle Disease / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D009522:Newcastle disease virus / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D021281:Quantitative Structure-Activity Relationship; D014760:Viral Fusion Proteins / Q000378:metabolism; D000099227:Abacavir
chemical_list: D000975:Antioxidants; D000998:Antiviral Agents; D015224:Dideoxynucleosides; D014760:Viral Fusion Proteins; D000099227:Abacavir
keywords: Abacavir; Antiviral activity; Chicken; Docking; Newcastle disease virus; Phosphorylation