title: Synthesis and Antiviral Activity of Novel Phosphorylated Derivatives of Didanosine Against Newcastle Disease Virus in Chicken.
abstract: A series of novel phosphorylated derivatives of didanosine were designed and docking studies were performed with a fusion protein of the Newcastle disease virus (NDV), to develop antiviral compounds against NDV. Based on the docking scores and binding affinities, three derivatives were selected. These compounds were synthesized and characterized by IR, (1) H, (13) C, (31) P, and CHN analysis and mass spectra. They were assessed for their in vitro antiviral activity in DF-1 cells; DDI-10 showed better antiviral activity as evidenced by significant reduction in plaque formation and cytopathic effects. DDI-10 was further evaluated in NDV-infected chicken; the survival rates and 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 1.5 mg/kg body weight of DDI-10 than with 3 mg/kg body weight of DDI. Further histopathological alterations in NDV-infected tissues were restored in chicken treated with DDI-10. Thus, based on the results from in silico, in vitro, and in vivo assays, the novel phosphorylated DDI-10 might be considered as potent antiviral compound for NDV infection in chicken.
authors.affiliation: Department of Biotechnology, Dravidian University, Kuppam, India.
authors.forename: Karanam Anandan
authors.initials: KA
authors.lastname: Suresh
authors.affiliation: Department of Biotechnology, Dravidian University, Kuppam, India.
authors.forename: Venkata Subbaiah C
authors.initials: VS
authors.lastname: Kadiam
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati, India.
authors.forename: Thaslim S K
authors.initials: TS
authors.lastname: Basha
authors.affiliation: Department of Chemistry, Sri Venkateswara University, Tirupati, India.
authors.forename: Naga Raju
authors.initials: NR
authors.lastname: Chamarti
authors.affiliation: Centre for Bioinformatics, Pondicherry University, Pondicherry, India.
authors.forename: Suresh M
authors.initials: SM
authors.lastname: Kumar
authors.affiliation: Department of Zoology, Sri Venkateswara University, Tirupati, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Wudayagiri
authors.affiliation: Department of Biotechnology, Dravidian University, Kuppam, India.
authors.forename: Lokanatha
authors.initials: L
authors.lastname: Valluru
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D002645:Chickens / Q000821:virology*; D016049:Didanosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006384:Hemagglutination / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D062105:Molecular Docking Simulation; D009521:Newcastle Disease / Q000188:drug therapy / Q000821:virology*; D009522:Newcastle disease virus / Q000187:drug effects*; D010766:Phosphorylation; D011201:Poultry Diseases / Q000188:drug therapy / Q000821:virology; D021281:Quantitative Structure-Activity Relationship; D013482:Superoxide Dismutase / Q000378:metabolism; D016019:Survival Analysis
chemical_list: D000998:Antiviral Agents; D002374:Catalase; D013482:Superoxide Dismutase; D016049:Didanosine
keywords: Antiviral activity; Chicken; Didanosine; Newcastle disease virus; QSAR studies