Structure-Guided Approach to Identify Potential Inhibitors of Large Envelope Protein to Prevent Hepatitis B Virus Infection.
Journal
Oxidative medicine and cellular longevity
ISSN: 1942-0994
Titre abrégé: Oxid Med Cell Longev
Pays: United States
ID NLM: 101479826
Informations de publication
Date de publication:
2019
2019
Historique:
received:
05
04
2019
revised:
10
06
2019
accepted:
02
07
2019
entrez:
28
11
2019
pubmed:
28
11
2019
medline:
11
4
2020
Statut:
epublish
Résumé
Hepatitis B virus (HBV) infection is one of the major causes of liver diseases, which can lead to hepatocellular carcinoma. The role of HBV envelope proteins is crucial in viral morphogenesis, infection, and propagation. Thus, blocking the pleiotropic functions of these proteins especially the PreS1 and PreS2 domains of the large surface protein (LHBs) is a promising strategy for designing efficient antivirals against HBV infection. Unfortunately, the structure of the LHBs protein has not been elucidated yet, and it seems that any structure-based drug discovery is critically dependent on this. To find effective inhibitors of LHBs, we have modeled and validated its three-dimensional structure and subsequently performed a virtual high-throughput screening against the ZINC database using RASPD and ParDOCK tools. We have identified four compounds, ZINC11882026, ZINC19741044, ZINC00653293, and ZINC15000762, showing appreciable binding affinity with the LHBs protein. The drug likeness was further validated using ADME screening and toxicity analysis. Interestingly, three of the four compounds showed the formation of hydrogen bonds with amino acid residues lying in the capsid binding region of the PreS1 domain of LHBs, suggesting the possibility of inhibiting the viral assembly and maturation process. The identification of potential lead molecules will help to discover more potent inhibitors with significant antiviral activities.
Identifiants
pubmed: 31772697
doi: 10.1155/2019/1297484
pmc: PMC6854180
doi:
Substances chimiques
Viral Envelope Proteins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1297484Informations de copyright
Copyright © 2019 Mahboubeh Mehmankhah et al.
Déclaration de conflit d'intérêts
The authors declare that they have no conflicts of interest.
Références
J Biol Chem. 2004 May 7;279(19):20108-17
pubmed: 14978030
Microb Cell. 2016 Sep 05;3(9):420-437
pubmed: 28357379
Phys Chem Chem Phys. 2013 Jun 21;15(23):9107-16
pubmed: 23646352
Semin Liver Dis. 2005;25 Suppl 1:9-19
pubmed: 16103977
Oncotarget. 2017 Jan 17;8(3):3895-3932
pubmed: 27965466
Mutat Res. 1994 Feb 1;305(1):47-61
pubmed: 7508547
Annu Rev Pathol. 2008;3:399-425
pubmed: 18039139
J Chem Inf Model. 2011 Oct 24;51(10):2515-27
pubmed: 21877713
Gastroenterology. 2009 Nov;137(5):1593-608.e1-2
pubmed: 19737565
Bioinformatics. 2000 Apr;16(4):404-5
pubmed: 10869041
Biochim Biophys Acta. 2016 Jan;1864(1):11-9
pubmed: 26478257
J Virol. 1988 Feb;62(2):407-16
pubmed: 3336067
Acta Biochim Pol. 2013;60(1):1-16
pubmed: 23513192
Oncotarget. 2016 Apr 26;7(17):23346-60
pubmed: 26992221
J Virol. 1998 Jul;72(7):5573-8
pubmed: 9621015
Protein Eng Des Sel. 2004 Apr;17(4):349-56
pubmed: 15115854
Gastroenterology. 2005 Jul;129(1):234-45
pubmed: 16012950
Nat Methods. 2015 Jan;12(1):7-8
pubmed: 25549265
Cancer Sci. 2006 Aug;97(8):683-8
pubmed: 16863502
EMBO J. 1995 Jan 16;14(2):247-56
pubmed: 7835336
J Virol. 2005 Feb;79(3):1613-22
pubmed: 15650187
Elife. 2012 Nov 13;1:e00049
pubmed: 23150796
Hepat Mon. 2016 Jun 28;16(7):e39097
pubmed: 27642350
J Comput Aided Mol Des. 2003 Dec;17(12):811-23
pubmed: 15124930
J Viral Hepat. 2017 Dec;24(12):1121-1131
pubmed: 28654219
Sci Rep. 2017 Mar 03;7:42717
pubmed: 28256516
Hepatology. 2007 Jul;46(1):254-65
pubmed: 17596850
Mikrobiyol Bul. 2018 Jan;52(1):23-34
pubmed: 29642827
J Phys Chem B. 2015 Aug 27;119(34):11136-45
pubmed: 26098815
Carcinogenesis. 2004 Oct;25(10):2023-32
pubmed: 15180947
FEBS Lett. 2005 Dec 5;579(29):6659-66
pubmed: 16307743
J Virol. 2005 Nov;79(21):13483-96
pubmed: 16227269
J Med Chem. 2003 Aug 14;46(17):3572-80
pubmed: 12904062
Protein Pept Lett. 2007;14(7):632-46
pubmed: 17897088
Nat Rev Drug Discov. 2003 Mar;2(3):192-204
pubmed: 12612645
Virus Genes. 2018 Feb;54(1):41-47
pubmed: 29119303
J Chem Inf Model. 2005 Jan-Feb;45(1):177-82
pubmed: 15667143
J Virol. 2009 Nov;83(22):11819-29
pubmed: 19740987
Gastroenterology. 2014 Jul;147(1):48-64
pubmed: 24768844
Data Brief. 2016 Jun 18;9:345-8
pubmed: 27672674
Hepatology. 2010 Mar;51(3):729-33
pubmed: 20186842
Sci Rep. 2015 Feb 12;5:8421
pubmed: 25672227
Clin Gastroenterol Hepatol. 2008 Dec;6(12):1315-41; quiz 1286
pubmed: 18845489
J Biol Chem. 2010 Dec 24;285(52):41074-86
pubmed: 20956535
Antivir Ther. 2010;15(3 Pt B):451-61
pubmed: 20516565
Int J Mol Sci. 2014 Feb 19;15(2):2892-905
pubmed: 24557582
Nat Biotechnol. 2008 Mar;26(3):335-41
pubmed: 18297057
Mol Cell Biochem. 2006 Oct;290(1-2):79-85
pubmed: 16960659
J Hepatol. 2015 Apr;62(4):791-8
pubmed: 25445396
J Viral Hepat. 2019 May;26(5):552-560
pubmed: 30576055
Adv Drug Deliv Rev. 2002 Mar 31;54(3):273-89
pubmed: 11922948
Mol Cell Biol. 2003 Oct;23(20):7198-209
pubmed: 14517290
Hepatology. 2009 May;49(5 Suppl):S13-21
pubmed: 19399811
J Med Chem. 2005 Apr 21;48(8):2725-55
pubmed: 15828810
J Virol. 2010 Apr;84(8):3879-88
pubmed: 20130049
World J Gastroenterol. 2009 Apr 14;15(14):1702-7
pubmed: 19360913
Curr Pharm Des. 2013;19(26):4687-700
pubmed: 23260020
J Chem Inf Model. 2012 Nov 26;52(11):3099-105
pubmed: 23092397
J Virol. 1999 Mar;73(3):2052-7
pubmed: 9971786
J Med Chem. 2004 Aug 26;47(18):4463-70
pubmed: 15317458
J Comput Aided Mol Des. 2016 Jul;30(7):533-9
pubmed: 27480697
Mol Cell. 2000 May;5(5):897-904
pubmed: 10882126
J Med Chem. 2000 Oct 19;43(21):3867-77
pubmed: 11052792