title: Virtual screening for oseltamivir-resistant a (H5N1) influenza neuraminidase from traditional Chinese medicine database: a combined molecular docking with molecular dynamics approach.
abstract: The neuraminidase (NA) of the influenza virus is the target of antiviral drug, oseltamivir. Recently, cases are reported that Influenza virus becoming resistant to oseltamivir, necessitating the development of new long-acting antiviral compounds. Most importantly, H274Y mutation in neuraminidase exhibits high levels of resistance to oseltamivir. In this report, a novel class of lead molecule with potential NA inhibitory activity was found from the traditional Chinese medicine database (TCMD) using virtual screening approach. Initially ADME properties of the lead compounds were analyzed with respect to the Lipinski rule of five. Subsequently, the data reduction was carried out by employing molecular docking study. Final validation was done by means of molecular dynamic simulations. The toxicity profiles for the screened compound were also analyzed. The result indicates that neoglucobrassicin (a compound derived from TCMD) become a promising lead compound and be effective in treating oseltamivir-resistant influenza virus strains.
authors: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology, Vellore, Tamil Nadu 632014 India.
authors: Vasudevan
authors: V
authors: Karthick
authors: Karuppasamy
authors: K
authors: Ramanathan
keywords: Molecular docking; Molecular dynamic simulation; Oseltamivir-resistance; Traditional Chinese medicine database (TCMD); Virtual screening
references: J Comput Chem. 2005 Dec;26(16):1701-18
references: 16211538
references: J Chem Theory Comput. 2008 Mar;4(3):435-47
references: 26620784
references: Proteins. 2005 Jan 1;58(1):119-25
references: 15521062
references: Clin Infect Dis. 2009 Jul 15;49(2):279-90
references: 19522652
references: Acta Crystallogr D Biol Crystallogr. 2004 Aug;60(Pt 8):1355-63
references: 15272157
references: PLoS Comput Biol. 2011 Dec;7(12):e1002315
references: 22215997
references: Mol Biosyst. 2011 Sep;7(9):2702-10
references: 21776525
references: Br Med Bull. 2006 May 01;75-76:63-80
references: 16651383
references: Chem Biol. 1999 May;6(5):319-31
references: 10322126
references: PLoS One. 2012;7(3):e33728
references: 22470466
references: Clin Microbiol Rev. 2007 Apr;20(2):243-67
references: 17428885
references: J Biomol Struct Dyn. 2011 Feb;28(4):471-82
references: 21142218
references: J Comput Aided Mol Des. 2011 Jun;25(6):525-31
references: 21647737
references: J Pharm Sci. 1999 Aug;88(8):807-14
references: 10430547
references: Appl Biochem Biotechnol. 2012 May;167(2):237-49
references: 22544690
references: J Biol Chem. 2010 Sep 10;285(37):28403-9
references: 20538598
references: PLoS One. 2011;6(12):e28793
references: 22174899
references: Nature. 1983 May 5-11;303(5912):41-4
references: 6188957
references: Nucleic Acids Res. 2000 Jan 1;28(1):235-42
references: 10592235
references: J Virol. 2007 Nov;81(22):12418-26
references: 17855542
references: Drug Discov Today. 2005 Nov 15;10(22):1497-500
references: 16257371
references: Nature. 2004 Dec 16;432(7019):862-5
references: 15602552
references: Bioorg Med Chem Lett. 2002 Jun 17;12(12):1647-50
references: 12039582
references: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references: 11259830
references: Med Res Rev. 2003 May;23(3):302-21
references: 12647312
references: Mol Biosyst. 2011 Dec;7(12):3366-74
references: 22012120
references: Curr Opin Chem Biol. 2004 Aug;8(4):349-58
references: 15288243
references: J Med Chem. 2000 Oct 5;43(20):3714-7
references: 11020286
references: Nature. 2006 Sep 7;443(7107):45-9
references: 16915235
references: PLoS One. 2011 Jan 06;6(1):e15939
references: 21253603
references: Structure. 1999 Mar 15;7(3):R55-60
references: 10368306
references: Biophys Chem. 2009 Nov;145(1):29-36
references: 19733000
references: BMC Biol. 2011 Oct 28;9:71
references: 22035460
references: Protein Eng. 1995 Feb;8(2):127-34
references: 7630882
references: Mol Biosyst. 2011 Sep;7(9):2711-9
references: 21796302
references: Annu Rev Biochem. 2000;69:531-69
references: 10966468
references: FEBS Lett. 2006 Mar 6;580(6):1649-53
references: 16494871
references: PLoS One. 2009 Jul 17;4(7):e6277
references: 19609439
references: J Med Chem. 2004 Dec 16;47(26):6529-40
references: 15588088
references: J Biomol Struct Dyn. 2011 Apr;28(5):773-86
references: 21294588
references: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W573-7
references: 17584799