Cover Image

Virion Protein 24 of Ebola Virus as a Potential Drug Target

Vivek Darapaneni

Abstract


The virion protein 24 of ebola Virus is multifunctional protein. The virion protein of ebola Virus plays imperative roles in the virus life cycle. The objective of the present study was to identify the residue conservation in the virion protein 24 of various ebola viruses. The study was based on 173 sequences from Bundibugyo, Sudan, Tai Forest, Zaire and Reston ebola viruses. The virion protein 24 showed higher level of sequence conservation. On the whole, this study exposed residues which are universally conserved among different viral species. These universally conserved residues might be involved in either structure stabilizing or protein-protein interactions. The conserved residues identified in the present study in conjunction with structural analysis of virion protein 24 identified novel binding sites: Ile157, Ile161, Leu164; Leu164, Leu167; Leu150, Ile161; Ala99, Ile161; Asp205, Ser207; Phe76, His78 and Glu46, Asp48. The present study could form basis for designing universal anti-ebola drugs which are resistant to mutations arising in the future.


Keywords


Conservation; Universally; Drugs; Mutation; Resistance; Anti-influenza

Full Text:

PDF

References


Mahanty S, Bray M. Pathogenesis of filoviral haemorrhagic fevers. Lancet Infect Dis. 2004, 4:487-498

Gire SK, Goba A, Andersen KG, Sealfon RS, Park DJ, Kanneh L, Jalloh S, Momoh M, Fullah M, et al. Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak. Science. 2014, 345:1369-1372

Burd EM. Ebola virus: a clear and present danger. J Clin Microbiol. 2015, 53:4-8

Sanchez A, Geisbert TW, Feldmann H. Filoviridae: Marburg and Ebola viruses. In: Fields Virology, ed. Knipe DM and Howley PM. Philadelphia: Lippincott Williams & Wilkins. 2007: 1410-1448

Kuhn JH, Becker S, Ebihara H, Geisbert TW, Johnson KM, Kawaoka Y, Lipkin WI, Negredo AI, et al. Proposal for a revised taxonomy of the family Filoviridae: classification, names of taxa and viruses, and virus abbreviations. Arch Virol. 2010, 155:2083-2103

Dolnik O, Kolesnikova L, Becker S: Filoviruses: Interactions with the host cell. Cell Mol Life Sci. 2008, 65(5): 756-776

Mateo M, Carbonnelle C, Reynard O, Kolesnikova L, Nemirov K, Page A, Volchkova VA, Volchkov VE. VP24 is a molecular determinant of Ebola virus virulence in guinea pigs. J Infect Dis. 2011, 204 (Suppl 3):S1011-S1020

Mateo M, Carbonnelle C, Martinez MJ, Reynard O, Page A, Volchkova VA, Volchkov VE. Knockdown of Ebola virus VP24 impairs viral nucleocapsid assembly and prevents virus replication. J Infect Dis. 2011, 204 (Suppl 3):S892-S896

Watanabe S, Noda T, Halfmann P, Jasenosky L, Kawaoka Y. Ebola virus (EBOV) VP24 inhibits transcription and replication of the EBOV genome. J Infect Dis. 2007, 196 (Suppl 2): S284-S290

Reid SP, Valmas C, Martinez O, Sanchez FM, Basler CF. Ebola virus VP24 proteins inhibit the interaction of NPI-1 subfamily karyopherin alpha proteins with activated STAT1. J Virol. 2007, 81(24): 13469-13477

Mateo M, Reid SP, Leung LW, Basler CF, Volchkov VE. Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling. J Virol. 2010, 84 (2): 1169-1175

Lee MS, Lebeda FJ, Olson MA. Fold prediction of VP24 protein of Ebola and Marburg viruses using de novo fragment assembly. J. Struct. Biol. 2009, 167 (2), 136-144

Ramanan P, Shabman RS, Brown CS, Amarasinghe GK, Basler CF, Leung DW. Filoviral immune evasion mechanisms. Viruses. 2011, 3 (9):1634-1649

Halfmann P, Neumann G, Kawaoka Y. The Ebolavirus VP24 protein blocks phosphorylation of p38 mitogen-activated protein kinase. J Infect Dis. 2011, 204 (Suppl 3):S953-S956

Shabman RS, Gulcicek EE, Stone KL, Basler CF. The Ebola virus VP24 protein prevents hnRNP C1/C2 binding to karyopherin α1 and partially alters its nuclear import. J Infect Dis. 2011, 204(Suppl 3):S904-S910

Mateo M, Reid SP, Leung LW, Basler CF, Volchkov VE. Ebolavirus VP24 binding to karyopherins is required for inhibition of interferon signaling. J Virol. 2010, 84:1169-1175

Xu W, Edwards MR, Borek DM, Feagins AR, Mittal A, Alinger JB, et al. Ebola Virus VP24 Targets a Unique NLS Binding Site on Karyopherin Alpha 5 to Selectively Compete with Nuclear Import of Phosphorylated STAT1. Cell Host Microbe. 2014, 16 (2):187-200

Han Z, Boshra H, Sunyer JO, Zwiers SH, Paragas J, Harty RN. Biochemical and Functional Characterization of the Ebola Virus VP24 Protein: Implications for a Role in Virus Assembly and Budding. J Virol. 2003, 77(3):1793-1800

Zhang APP, Abelson DM, Bornholdt ZA, Liu T, Woods VL Jr, Saphire EO. The ebolavirus VP24 interferon antagonist Know your enemy. Virulence. 2012, 3(5):440-445

Brister JR, Bao Y, Zhdanov SA, Ostapchuck Y, Chetvernin V, Kiryutin B, Zaslavsky L, Kimelman M, Tatusova TA. Virus Variation Resource - recent updates and future directions. Nucleic Acids Res. 2014, 42(Database issue):D660-D665

Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high through-put. Nucleic Acids Res. 2004, 32: 1792-1797

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE. The Protein Data Bank. Nucleic Acids Res. 2000, 28(1): 235-42

Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T, Ben-Tal N. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucl Acids Res. 2005, 33: W299-W302

Glaser F, Pupko T, Paz I, Bell RE, Bechor D, Martz E, Ben-Tal N. ConSurf: Identification of Functional Regions in Proteins by Surface-Mapping of Phylogenetic information. Bioinformatics. 2003, 19:163-164

Ashkenazy H, Erez E, Martz E, Pupko T, Ben-Tal, N. ConSurf 2010: calculating Evolutionary conservation in sequence and structure of proteins and nucleic acids. Nucleic Acids Res. 2010 38:W529-W533

Celniker G, Nimrod G, Ashkenazy H, Glaser F, Martz E, Mayrose I, Pupko T, Ben-Tal, N. ConSurf: Using Evolutionary Data to Raise Testable Hypotheses about Protein Function. Israel Journal of Chemistry. 2013, 53(3-4):199-206

Roy A, Zhang Y. Recognizing protein-ligand binding sites by global structural alignment and local geometry refinement. Structure. 2012, 20: 987-997

Roy A, Yang J, Zhang. COFACTOR: an accurate comparative algorithm for structure-based protein function annotation. Nucleic Acids Research. 2012, 40: W471-W477

Yang J, Roy A, Zhang Y. BioLiP: a semi-manually curated database for biologically relevant ligand-protein interactions. Nucleic Acids Research. 2013, 41:D1096-D1103

Yang J, Roy A, Zhang Y. Protein–ligand binding site recognition using complementary binding-specific substructure comparison and sequence profile alignment. Bioinformatics. 2013, 29 ( 20): 2588-2595

Hernandez M, Ghersi D, Sanchez R. SITEHOUND-web: a server for ligand binding Site identification in protein structures. Nucleic Acids Res. 2009, 37: W413-W416

Schueler-Furman O, Baker D. Conserved residue clustering and protein structure prediction. Proteins. 2003, 52:225-235


Refbacks

  • There are currently no refbacks.


AJCMicrob (ISSN 2572-5815) Copyright © 2012-2020. All rights reserved. Published by Ivy Union Publishing, 3204 Valley Rush Dr, Apex, North Carolina 27502, United States