In Silico Identification of New Targets for Diagnosis, Vaccine, and Drug Candidates against Trypanosoma cruzi
Autor: | Arun Kumar Jaiswal, Carlo José Freire Oliveira, Letícia de Castro Oliveira, Thiago de Jesus Sousa, Lúcio Roberto Cançado Castellano, Siomar de Castro Soares, Malu Mateus Santos, Leandro Gomes Alves, Juliana Cristina Costa-Madeira, Marcos Vinicius da Silva, Chamberttan Souza Desidério, Virmondes Rodrigues Junior, Mariana de Oliveira-Silva, Rafael Obata Trevisan, Weslley Guimarães Bovi, Vasco Azevedo, Sandeep Tiwari |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Chagas disease Medicine (General) Article Subject In silico 030106 microbiology Clinical Biochemistry Computational biology Epitope 03 medical and health sciences R5-920 Antigen parasitic diseases MHC class I Genetics medicine Trypanosoma cruzi Molecular Biology biology Biochemistry (medical) Reverse vaccinology General Medicine medicine.disease biology.organism_classification 030104 developmental biology GenBank biology.protein Research Article |
Zdroj: | Disease Markers Disease Markers, Vol 2020 (2020) |
ISSN: | 1875-8630 0278-0240 |
Popis: | 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. |
Databáze: | OpenAIRE |
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