Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations

Detalhes bibliográficos
Autor(a) principal: Siqueira, Andrei Santos
Data de Publicação: 2017
Outros Autores: Lima, Alex Ranieri Jerônimo, Souza, Rafael Conceição de, Santos, Alberdan Silva, Vianez Júnior, João Lídio da Silva Gonçalves, Gonçalves, Evonnildo Costa
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
Texto Completo: https://patua.iec.gov.br/handle/iec/2882
Resumo: The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations. It was possible to identify the key residues for protein-ligand interaction such as Glu10, Ala11, Pro17, Ans18, Arg30, Thr41, Ser42 and Arg43, which also has importance action against HIV. All binding free energy calculations showed negative values to ΔGbind of protein-DENV carbohydrate complexation. Additionally, these results are similar to the values of scytovirin and HIV gp120 carbohydrate complexation (-32.20 kcal/mol). Furthermore, we found that SD1 individually has more affinity to the carbohydrate and the Asn9, Glu10, Asn18, Arg30 and Arg43 demonstrated an important role in this matter. We also found that mutant G48R has better affinity (-34.10 kcal/mol) for the DENV carbohydrate than the wild type protein (-27.15 kcal/mol).
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spelling Siqueira, Andrei SantosLima, Alex Ranieri JerônimoSouza, Rafael Conceição deSantos, Alberdan SilvaVianez Júnior, João Lídio da Silva GonçalvesGonçalves, Evonnildo Costa2017-11-24T18:56:15Z2017-11-24T18:56:15Z2017SIQUEIRA, Andrei Santos et al. Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations. Biochemical and Biophysical Research Communications, v. 490, n. 3, p. 1033-1038, Aug. 2017.0006-291Xhttps://patua.iec.gov.br/handle/iec/288210.1016/j.bbrc.2017.06.160The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations. It was possible to identify the key residues for protein-ligand interaction such as Glu10, Ala11, Pro17, Ans18, Arg30, Thr41, Ser42 and Arg43, which also has importance action against HIV. All binding free energy calculations showed negative values to ΔGbind of protein-DENV carbohydrate complexation. Additionally, these results are similar to the values of scytovirin and HIV gp120 carbohydrate complexation (-32.20 kcal/mol). Furthermore, we found that SD1 individually has more affinity to the carbohydrate and the Asn9, Glu10, Asn18, Arg30 and Arg43 demonstrated an important role in this matter. We also found that mutant G48R has better affinity (-34.10 kcal/mol) for the DENV carbohydrate than the wild type protein (-27.15 kcal/mol).Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro de Inovações Tecnológicas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Naturais. Laboratórios de Investigação Sistemática em Biotecnologia e Biodiversidade Molecular. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Centro de Inovações Tecnológicas. Ananindeua, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Tecnologia Biomolecular. Belém, PA, Brazil.engElsevierAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculationsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleAntivirais / farmacologiaProteínas de Bactérias / farmacologiaProteínas de Transporte / farmacologiaCianobactérias / químicaDengue / terapiaVírus da Dengue / efeitos de drogasLectinas / farmacologiaProteínas do Envelope Viral / metabolismoMutação PuntualLigação ProteicaSimulação de Dinâmica MolecularTemperatura Ambienteinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECLICENSElicense.txtlicense.txttext/plain; charset=utf-871https://patua.iec.gov.br/bitstreams/cde35862-78fa-4f5f-8080-50a29bf389b6/download52f1732ea66fbd1123abe39f5373b797MD52ORIGINALAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdfAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdfapplication/pdf135659https://patua.iec.gov.br/bitstreams/b71083f6-ad5f-4e91-a7c5-5c4d8cce8421/download5b176be161c72009488d702f404f2802MD53TEXTAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.txtAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.txtExtracted texttext/plain4813https://patua.iec.gov.br/bitstreams/05b02da3-1167-4063-90a0-f90d69176154/downloada7fd799765bcd59cf166692899228642MD56THUMBNAILAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.jpgAnti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations.pdf.jpgGenerated Thumbnailimage/jpeg6090https://patua.iec.gov.br/bitstreams/87764e73-8ac3-4756-bf95-d12d38be19fe/downloadc78e658907e21112946b23471e0ee73fMD57iec/28822022-10-21 00:34:46.459oai:patua.iec.gov.br:iec/2882https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2022-10-21T00:34:46Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)falseVG9kb3Mgb3MgZG9jdW1lbnRvcyBkZXNzYSBjb2xlw6fDo28gc2VndWVtIGEgTGljZW7Dp2EgQ3JlYXRpdmUgY29tbW9ucy4=
dc.title.pt_BR.fl_str_mv Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
title Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
spellingShingle Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
Siqueira, Andrei Santos
Antivirais / farmacologia
Proteínas de Bactérias / farmacologia
Proteínas de Transporte / farmacologia
Cianobactérias / química
Dengue / terapia
Vírus da Dengue / efeitos de drogas
Lectinas / farmacologia
Proteínas do Envelope Viral / metabolismo
Mutação Puntual
Ligação Proteica
Simulação de Dinâmica Molecular
Temperatura Ambiente
title_short Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
title_full Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
title_fullStr Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
title_full_unstemmed Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
title_sort Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations
author Siqueira, Andrei Santos
author_facet Siqueira, Andrei Santos
Lima, Alex Ranieri Jerônimo
Souza, Rafael Conceição de
Santos, Alberdan Silva
Vianez Júnior, João Lídio da Silva Gonçalves
Gonçalves, Evonnildo Costa
author_role author
author2 Lima, Alex Ranieri Jerônimo
Souza, Rafael Conceição de
Santos, Alberdan Silva
Vianez Júnior, João Lídio da Silva Gonçalves
Gonçalves, Evonnildo Costa
author2_role author
author
author
author
author
dc.contributor.author.fl_str_mv Siqueira, Andrei Santos
Lima, Alex Ranieri Jerônimo
Souza, Rafael Conceição de
Santos, Alberdan Silva
Vianez Júnior, João Lídio da Silva Gonçalves
Gonçalves, Evonnildo Costa
dc.subject.decsPrimary.pt_BR.fl_str_mv Antivirais / farmacologia
Proteínas de Bactérias / farmacologia
Proteínas de Transporte / farmacologia
Cianobactérias / química
Dengue / terapia
Vírus da Dengue / efeitos de drogas
Lectinas / farmacologia
Proteínas do Envelope Viral / metabolismo
Mutação Puntual
Ligação Proteica
Simulação de Dinâmica Molecular
Temperatura Ambiente
topic Antivirais / farmacologia
Proteínas de Bactérias / farmacologia
Proteínas de Transporte / farmacologia
Cianobactérias / química
Dengue / terapia
Vírus da Dengue / efeitos de drogas
Lectinas / farmacologia
Proteínas do Envelope Viral / metabolismo
Mutação Puntual
Ligação Proteica
Simulação de Dinâmica Molecular
Temperatura Ambiente
description The absence of a specific treatment against DENV has led to intensive research into developing strategies for curing the infection. One lectin with high antiviral activity is scytovirin, which was isolated from the cyanobacterium Scytonema varium and has proven activity against HIV and Zaire Ebola Virus. To achieve the results presented here, we tested the affinity of full-length scytovirin, SD1 and SD2 separately, and six SD1 mutants for DENV glycoprotein E carbohydrate by Molecular Dynamics (MD) simulations and binding free energy calculations. It was possible to identify the key residues for protein-ligand interaction such as Glu10, Ala11, Pro17, Ans18, Arg30, Thr41, Ser42 and Arg43, which also has importance action against HIV. All binding free energy calculations showed negative values to ΔGbind of protein-DENV carbohydrate complexation. Additionally, these results are similar to the values of scytovirin and HIV gp120 carbohydrate complexation (-32.20 kcal/mol). Furthermore, we found that SD1 individually has more affinity to the carbohydrate and the Asn9, Glu10, Asn18, Arg30 and Arg43 demonstrated an important role in this matter. We also found that mutant G48R has better affinity (-34.10 kcal/mol) for the DENV carbohydrate than the wild type protein (-27.15 kcal/mol).
publishDate 2017
dc.date.accessioned.fl_str_mv 2017-11-24T18:56:15Z
dc.date.available.fl_str_mv 2017-11-24T18:56:15Z
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dc.identifier.citation.fl_str_mv SIQUEIRA, Andrei Santos et al. Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations. Biochemical and Biophysical Research Communications, v. 490, n. 3, p. 1033-1038, Aug. 2017.
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/2882
dc.identifier.issn.-.fl_str_mv 0006-291X
dc.identifier.doi.-.fl_str_mv 10.1016/j.bbrc.2017.06.160
identifier_str_mv SIQUEIRA, Andrei Santos et al. Anti-dengue virus activity of scytovirin and evaluation of point mutation effects by molecular dynamics and binding free energy calculations. Biochemical and Biophysical Research Communications, v. 490, n. 3, p. 1033-1038, Aug. 2017.
0006-291X
10.1016/j.bbrc.2017.06.160
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