title: Antiviral potential of 4-hydroxypanduratin A, secondary metabolite of Fingerroot, Boesenbergia pandurata (Schult.), towards Japanese Encephalitis virus NS2B/NS3 protease.
abstract: 4-hydroxypanduratin A is a secondary metabolite of Boesenbergia pandurata Schult. (Fingerroot) plant with various pharmacological activities such as neuroprotective, potent antioxidant, antibacterial and antifungal. Flaviviral NS2B/NS3 protease activity is essential for polyprotein processing and viral replication for Japanese Encephalitis Virus (JEV), a major cause of Acute Encephaltis in Asia. Inhibition of formation of this complex by arresting the binding of NS2B with NS3 would reduce the enzyme's activity to meager proportions and hence would prevent further viral proliferation. The automated 3D structure of NS2B protein of the JEV GP78 was predicted based on the sequence-to-structure-to-function paradigm using I-TASSER and the function of NS2B protein was inferred by matching to other known proteins. The stereochemical quality of predicted structure was checked by PROCHECK. The antiviral activity of 4-hydroxypanduratin A against NS2B protein as a potential drug has been elucidated in this paper. Docking simulation analysis showed 4-hydroxypanduratin A as potential inhibitor of NS2B protein/cofactor which is necessary for NS3 protease activity. 220 derivatives of 4-hydroxypanduratin A were virtually screened with rigid criteria of Lipinski's rule of 5 using Autodock4.2. 4-hydroxypanduratin A was found interacting with target hydrophilic domain in NS2B protein by two Hbonds (Gly80 and Asp81) with active residues, several hydrophobic interactions, Log P value of 5.6, inhibition constant (Ki) of 51.07nM and lowest binding energy of -9.95Kcal/Mol. Hence, 4-hydroxypanduratin A targeted to Site 2 will have sufficient profound effect to inhibit protease activity to abrogate viral replication. It could be a promising potential drug candidate for JEV infections using NS2B Site 2 as a Drug target.
authors: Department of Biotechnology, Madhav Institute of Technology and Science, Race Course Road, Gola Ka Mandir, Gwalior (M.P.) India.
authors: Chandrabhan
authors: C
authors: Seniya
authors: Harshal
authors: H
authors: Mishra
authors: Ajay
authors: A
authors: Yadav
authors: Nitin
authors: N
authors: Sagar
authors: Babita
authors: B
authors: Chaturvedi
authors: Kuldeep
authors: K
authors: Uchadia
authors: Gulshan
authors: G
authors: Wadhwa
keywords: 4- hydroxypanduratin A; I-TASSER; Japanese Encephalitis Virus; Molecular Docking; NS2B/NS3 protease; Structure prediction
references: Proc Natl Acad Sci U S A. 2004 May 18;101(20):7594-9
references: 15126668
references: Biosci Biotechnol Biochem. 2006 Sep;70(9):2281-4
references: 16960369
references: Bioinformation. 2012;8(3):134-41
references: 22368385
references: J Gen Virol. 1999 Jul;80 ( Pt 7):1665-1671
references: 10423134
references: FEBS J. 2006 Aug;273(16):3650-62
references: 16911516
references: BMC Bioinformatics. 2008 Jan 23;9:40
references: 18215316
references: Bioinformation. 2012;8(14):678-83
references: 23055609
references: J Gen Virol. 2008 Apr;89(Pt 4):1010-1014
references: 18343843
references: J Chem Inf Model. 2007 Jul-Aug;47(4):1481-92
references: 17585754
references: Planta Med. 2003 Dec;69(12):1102-8
references: 14750025
references: J Biomol NMR. 1996 Dec;8(4):477-86
references: 9008363
references: Virology. 1989 Apr;169(2):365-76
references: 2705302
references: Nucleic Acids Res. 2007;35(10):3375-82
references: 17478507
references: Nucleic Acids Res. 2005 Apr 22;33(7):2302-9
references: 15849316
references: Bioinformation. 2010 Nov 27;5(6):250-4
references: 21364826
references: Protein Sci. 2007 Oct;16(10):2294-300
references: 17893366
references: Toxicon. 2001 May;39(5):603-13
references: 11072038
references: Science. 1985 Aug 23;229(4715):726-33
references: 4023707
references: J Mol Biol. 1999 Sep 17;292(2):195-202
references: 10493868
references: J Mol Biol. 1993 Dec 5;234(3):779-815
references: 8254673
references: J Comput Chem. 2009 Dec;30(16):2785-91
references: 19399780
references: Nat Protoc. 2010 Apr;5(4):725-38
references: 20360767
references: Annu Rev Microbiol. 1990;44:649-88
references: 2174669
references: Nat Med. 2004 Dec;10(12 Suppl):S98-109
references: 15577938
references: Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):3-26
references: 11259830
references: J Virol. 1989 Aug;63(8):3345-52
references: 2501515
references: Nat Struct Mol Biol. 2006 Apr;13(4):372-3
references: 16532006
references: J Agric Food Chem. 2002 Dec 4;50(25):7472-6
references: 12452678
references: Bioorg Med Chem Lett. 2006 Jun 15;16(12):3337-40
references: 16621533
references: J Comput Chem. 2004 Apr 30;25(6):865-71
references: 15011258
references: Biophys J. 2003 Aug;85(2):1145-64
references: 12885659
references: J Gen Virol. 1995 Mar;76 ( Pt 3):573-80
references: 7897348
references: Protein Sci. 2007 May;16(5):795-806
references: 17400917
references: Phytochemistry. 2002 Jan;59(2):169-73
references: 11809452
references: Int J Mol Sci. 2011 Feb 09;12(2):1089-100
references: 21541045
references: J Virol. 2003 Mar;77(5):3091-8
references: 12584335
references: J Virol. 1993 Apr;67(4):2034-42
references: 8383225
references: Proteins. 2012 Jul;80(7):1715-35
references: 22411565
references: BMC Biol. 2007 May 08;5:17
references: 17488521