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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...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787821/ https://www.ncbi.nlm.nih.gov/pubmed/33488847 http://dx.doi.org/10.1155/2020/9130719 |
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author | Trevisan, Rafael Obata Santos, Malú Mateus Desidério, Chamberttan Souza Alves, Leandro Gomes de Jesus Sousa, Thiago de Castro Oliveira, Letícia Jaiswal, Arun Kumar Tiwari, Sandeep Bovi, Weslley Guimarães de Oliveira-Silva, Mariana Costa-Madeira, Juliana Cristina Castellano, Lúcio Roberto Cançado Silva, Marcos Vinicius Azevedo, Vasco Rodrigues Junior, Virmondes Oliveira, Carlo José Freire de Castro Soares, Siomar |
author_facet | Trevisan, Rafael Obata Santos, Malú Mateus Desidério, Chamberttan Souza Alves, Leandro Gomes de Jesus Sousa, Thiago de Castro Oliveira, Letícia Jaiswal, Arun Kumar Tiwari, Sandeep Bovi, Weslley Guimarães de Oliveira-Silva, Mariana Costa-Madeira, Juliana Cristina Castellano, Lúcio Roberto Cançado Silva, Marcos Vinicius Azevedo, Vasco Rodrigues Junior, Virmondes Oliveira, Carlo José Freire de Castro Soares, Siomar |
author_sort | Trevisan, Rafael Obata |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-7787821 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-77878212021-01-22 In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi Trevisan, Rafael Obata Santos, Malú Mateus Desidério, Chamberttan Souza Alves, Leandro Gomes de Jesus Sousa, Thiago de Castro Oliveira, Letícia Jaiswal, Arun Kumar Tiwari, Sandeep Bovi, Weslley Guimarães de Oliveira-Silva, Mariana Costa-Madeira, Juliana Cristina Castellano, Lúcio Roberto Cançado Silva, Marcos Vinicius Azevedo, Vasco Rodrigues Junior, Virmondes Oliveira, Carlo José Freire de Castro Soares, Siomar Dis Markers Research Article 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. Hindawi 2020-12-10 /pmc/articles/PMC7787821/ /pubmed/33488847 http://dx.doi.org/10.1155/2020/9130719 Text en Copyright © 2020 Rafael Obata Trevisan et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Trevisan, Rafael Obata Santos, Malú Mateus Desidério, Chamberttan Souza Alves, Leandro Gomes de Jesus Sousa, Thiago de Castro Oliveira, Letícia Jaiswal, Arun Kumar Tiwari, Sandeep Bovi, Weslley Guimarães de Oliveira-Silva, Mariana Costa-Madeira, Juliana Cristina Castellano, Lúcio Roberto Cançado Silva, Marcos Vinicius Azevedo, Vasco Rodrigues Junior, Virmondes Oliveira, Carlo José Freire de Castro Soares, Siomar In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi |
title |
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_short |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787821/ https://www.ncbi.nlm.nih.gov/pubmed/33488847 http://dx.doi.org/10.1155/2020/9130719 |
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