In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi
Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Despite the efforts and distinct methodologies, the search of antigens for diagnosis, vaccine, and drug targets for the disease is still needed. The present study is aimed at identifying possible antigens that c...
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Language: | English |
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Hindawi Limited
2020-01-01
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Series: | Disease Markers |
Online Access: | http://dx.doi.org/10.1155/2020/9130719 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rafael Obata Trevisan Malú Mateus Santos Chamberttan Souza Desidério Leandro Gomes Alves Thiago de Jesus Sousa Letícia de Castro Oliveira Arun Kumar Jaiswal Sandeep Tiwari Weslley Guimarães Bovi Mariana de Oliveira-Silva Juliana Cristina Costa-Madeira Lúcio Roberto Cançado Castellano Marcos Vinicius Silva Vasco Azevedo Virmondes Rodrigues Junior Carlo José Freire Oliveira Siomar de Castro Soares |
spellingShingle |
Rafael Obata Trevisan Malú Mateus Santos Chamberttan Souza Desidério Leandro Gomes Alves Thiago de Jesus Sousa Letícia de Castro Oliveira Arun Kumar Jaiswal Sandeep Tiwari Weslley Guimarães Bovi Mariana de Oliveira-Silva Juliana Cristina Costa-Madeira Lúcio Roberto Cançado Castellano Marcos Vinicius Silva Vasco Azevedo Virmondes Rodrigues Junior Carlo José Freire Oliveira Siomar de Castro Soares In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi Disease Markers |
author_facet |
Rafael Obata Trevisan Malú Mateus Santos Chamberttan Souza Desidério Leandro Gomes Alves Thiago de Jesus Sousa Letícia de Castro Oliveira Arun Kumar Jaiswal Sandeep Tiwari Weslley Guimarães Bovi Mariana de Oliveira-Silva Juliana Cristina Costa-Madeira Lúcio Roberto Cançado Castellano Marcos Vinicius Silva Vasco Azevedo Virmondes Rodrigues Junior Carlo José Freire Oliveira Siomar de Castro Soares |
author_sort |
Rafael Obata Trevisan |
title |
In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi |
title_short |
In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi |
title_full |
In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi |
title_fullStr |
In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi |
title_full_unstemmed |
In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi |
title_sort |
in silico identification of new targets for diagnosis, vaccine, and drug candidates against trypanosoma cruzi |
publisher |
Hindawi Limited |
series |
Disease Markers |
issn |
0278-0240 1875-8630 |
publishDate |
2020-01-01 |
description |
Chagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Despite the efforts and distinct methodologies, the search of antigens for diagnosis, vaccine, and drug targets for the disease is still needed. The present study is aimed at identifying possible antigens that could be used for diagnosis, vaccine, and drugs targets against T. cruzi using reverse vaccinology and molecular docking. The genomes of 28 T. cruzi strains available in GenBank (NCBI) were used to obtain the genomic core. Then, subtractive genomics was carried out to identify nonhomologous genes to the host in the core. A total of 2630 conserved proteins in 28 strains of T. cruzi were predicted using OrthoFinder and Diamond software, in which 515 showed no homology to the human host. These proteins were evaluated for their subcellular localization, from which 214 are cytoplasmic and 117 are secreted or present in the plasma membrane. To identify the antigens for diagnosis and vaccine targets, we used the VaxiJen software, and 14 nonhomologous proteins were selected showing high binding efficiency with MHC I and MHC II with potential for in vitro and in vivo tests. When these 14 nonhomologous molecules were compared against other trypanosomatids, it was found that the retrotransposon hot spot (RHS) protein is specific only for T. cruzi parasite suggesting that it could be used for Chagas diagnosis. Such 14 proteins were analyzed using the IEDB software to predict their epitopes in both B and T lymphocytes. Furthermore, molecular docking analysis was performed using the software MHOLline. As a result, we identified 6 possible T. cruzi drug targets that could interact with 4 compounds already known as antiparasitic activities. These 14 protein targets, along with 6 potential drug candidates, can be further validated in future studies, in vivo, regarding Chagas disease. |
url |
http://dx.doi.org/10.1155/2020/9130719 |
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doaj-9fcb387389a04b4aa2722b7cd94e87e72020-12-21T11:41:26ZengHindawi LimitedDisease Markers0278-02401875-86302020-01-01202010.1155/2020/91307199130719In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruziRafael Obata Trevisan0Malú Mateus Santos1Chamberttan Souza Desidério2Leandro Gomes Alves3Thiago de Jesus Sousa4Letícia de Castro Oliveira5Arun Kumar Jaiswal6Sandeep Tiwari7Weslley Guimarães Bovi8Mariana de Oliveira-Silva9Juliana Cristina Costa-Madeira10Lúcio Roberto Cançado Castellano11Marcos Vinicius Silva12Vasco Azevedo13Virmondes Rodrigues Junior14Carlo José Freire Oliveira15Siomar de Castro Soares16Department of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Genetics, Ecology and Evolution, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Genetics, Ecology and Evolution, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilHuman Immunology Research and Education Group-GEPIH, Technical School of Health, Federal University of Paraíba, João Pessoa, Paraíba, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Genetics, Ecology and Evolution, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilDepartment of Microbiology, Immunology and Parasitology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, BrazilChagas disease is a neglected tropical disease caused by the parasite Trypanosoma cruzi. Despite the efforts and distinct methodologies, the search of antigens for diagnosis, vaccine, and drug targets for the disease is still needed. The present study is aimed at identifying possible antigens that could be used for diagnosis, vaccine, and drugs targets against T. cruzi using reverse vaccinology and molecular docking. The genomes of 28 T. cruzi strains available in GenBank (NCBI) were used to obtain the genomic core. Then, subtractive genomics was carried out to identify nonhomologous genes to the host in the core. A total of 2630 conserved proteins in 28 strains of T. cruzi were predicted using OrthoFinder and Diamond software, in which 515 showed no homology to the human host. These proteins were evaluated for their subcellular localization, from which 214 are cytoplasmic and 117 are secreted or present in the plasma membrane. To identify the antigens for diagnosis and vaccine targets, we used the VaxiJen software, and 14 nonhomologous proteins were selected showing high binding efficiency with MHC I and MHC II with potential for in vitro and in vivo tests. When these 14 nonhomologous molecules were compared against other trypanosomatids, it was found that the retrotransposon hot spot (RHS) protein is specific only for T. cruzi parasite suggesting that it could be used for Chagas diagnosis. Such 14 proteins were analyzed using the IEDB software to predict their epitopes in both B and T lymphocytes. Furthermore, molecular docking analysis was performed using the software MHOLline. As a result, we identified 6 possible T. cruzi drug targets that could interact with 4 compounds already known as antiparasitic activities. These 14 protein targets, along with 6 potential drug candidates, can be further validated in future studies, in vivo, regarding Chagas disease.http://dx.doi.org/10.1155/2020/9130719 |