Synthesis and Antiviral Activity of Novel Phosphorylated Derivatives of Didanosine Against Newcastle Disease Virus in Chicken

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. The...

Full description

Saved in:

Bibliographic Details
Published in:	Archiv der Pharmazie (Weinheim) Vol. 349; no. 6; pp. 442 - 455
Main Authors:	Suresh, Karanam Anandan, Kadiam, Venkata Subbaiah C., Basha, Thaslim S. K., Chamarti, Naga Raju, Kumar, Suresh M., Wudayagiri, Rajendra, Valluru, Lokanatha
Format:	Journal Article
Language:	English
Published:	Germany Blackwell Publishing Ltd 01-06-2016 Wiley Subscription Services, Inc
Subjects:	Animals Antiviral activity Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Antiviral Agents - therapeutic use Brain - metabolism Catalase - metabolism Cells, Cultured Chicken Chickens - virology Didanosine Didanosine - analogs & derivatives Didanosine - chemistry Didanosine - pharmacology Didanosine - therapeutic use Hemagglutination - drug effects Lipid Peroxidation - drug effects Liver - metabolism Lung - metabolism Molecular Docking Simulation Newcastle Disease - drug therapy Newcastle Disease - virology Newcastle disease virus Newcastle disease virus - drug effects Phosphorylation Poultry Diseases - drug therapy Poultry Diseases - virology QSAR studies Quantitative Structure-Activity Relationship Superoxide Dismutase - metabolism Survival Analysis Chicken QSAR studies Newcastle disease virus Didanosine Antiviral activity
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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, 1H, 13C, 31P, 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. Novel phosphorylated derivatives of didanosine were designed and docking studies were performed with a fusion protein of the Newcastle disease virus (NDV). DDI‐10 showed antiviral activity as evidenced by significant reduction in plaque formation and cytopathic effects. Histopathological alterations in NDV‐infected tissues were restored in DDI‐10‐treated chicken. DDI‐10 may thus be a potent antiviral compound for NDV infection in chicken.
Bibliography:	ArticleID:ARDP201600038 istex:F3B0789E30DCE6BFE9E04DA6F094E4AFB29C0990 ark:/67375/WNG-V7NK1H54-V SERB - No. SR/SO/AS-021/2013 dt.29.11.2013 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0365-6233 1521-4184
DOI:	10.1002/ardp.201600038