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Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase

OBJECTIVE: The low investment in research, diagnosis and treatment are factors that contribute to the continuity of Chagas’ disease as a neglected tropical diseases (NTDs). In this context, the repositioning of drugs represents a useful strategy, in the search for new chemotherapeutic approaches for...

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Autores principales: Castilho, Vanessa V. S., Gonçalves, Keyla C. S., Rebello, Karina M., Baptista, Luiz P. R., Sangenito, Leandro S., Santos, Helena L. C., Branquinha, Marta H., Santos, André L. S., Menna-Barreto, Rubem F. S., Guimarães, Ana C., d’Avila-Levy, Claudia M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249910/
https://www.ncbi.nlm.nih.gov/pubmed/30463602
http://dx.doi.org/10.1186/s13104-018-3927-z
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author Castilho, Vanessa V. S.
Gonçalves, Keyla C. S.
Rebello, Karina M.
Baptista, Luiz P. R.
Sangenito, Leandro S.
Santos, Helena L. C.
Branquinha, Marta H.
Santos, André L. S.
Menna-Barreto, Rubem F. S.
Guimarães, Ana C.
d’Avila-Levy, Claudia M.
author_facet Castilho, Vanessa V. S.
Gonçalves, Keyla C. S.
Rebello, Karina M.
Baptista, Luiz P. R.
Sangenito, Leandro S.
Santos, Helena L. C.
Branquinha, Marta H.
Santos, André L. S.
Menna-Barreto, Rubem F. S.
Guimarães, Ana C.
d’Avila-Levy, Claudia M.
author_sort Castilho, Vanessa V. S.
collection PubMed
description OBJECTIVE: The low investment in research, diagnosis and treatment are factors that contribute to the continuity of Chagas’ disease as a neglected tropical diseases (NTDs). In this context, the repositioning of drugs represents a useful strategy, in the search for new chemotherapeutic approaches for NTDs. HIV aspartic peptidase inhibitors (HIV IPs) are good candidates for drug repurposing. Here, we modeled the three dimensional structure of an aspartyl peptidase of Trypanosoma cruzi, the causative agent of Chagas’ disease, aligned it to the HIV aspartyl peptidase and performed docking binding assays with the HIV PIs. RESULTS: The 3D structure confirmed the presence of acid aspartic residues, which are critical to enzyme activity. The docking experiment revealed that HIV IPs bind to the active site of the enzyme, being ritonavir and lopinavir the ones with greater affinity. Benznidazole presented the worst binding affinity, this drug is currently used in Chagas’ disease treatment and was included as negative control. These results together with previous data on the trypanocidal effect of the HIV PIs support the hypothesis that a T. cruzi aspartyl peptidase can be the intracellular target of these inhibitors. However, the direct demonstration of the inhibition of T. cruzi aspartyl peptidase activity by HIV PIs is still a goal to be persuaded. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3927-z) contains supplementary material, which is available to authorized users.
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spelling pubmed-62499102018-11-26 Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase Castilho, Vanessa V. S. Gonçalves, Keyla C. S. Rebello, Karina M. Baptista, Luiz P. R. Sangenito, Leandro S. Santos, Helena L. C. Branquinha, Marta H. Santos, André L. S. Menna-Barreto, Rubem F. S. Guimarães, Ana C. d’Avila-Levy, Claudia M. BMC Res Notes Research Note OBJECTIVE: The low investment in research, diagnosis and treatment are factors that contribute to the continuity of Chagas’ disease as a neglected tropical diseases (NTDs). In this context, the repositioning of drugs represents a useful strategy, in the search for new chemotherapeutic approaches for NTDs. HIV aspartic peptidase inhibitors (HIV IPs) are good candidates for drug repurposing. Here, we modeled the three dimensional structure of an aspartyl peptidase of Trypanosoma cruzi, the causative agent of Chagas’ disease, aligned it to the HIV aspartyl peptidase and performed docking binding assays with the HIV PIs. RESULTS: The 3D structure confirmed the presence of acid aspartic residues, which are critical to enzyme activity. The docking experiment revealed that HIV IPs bind to the active site of the enzyme, being ritonavir and lopinavir the ones with greater affinity. Benznidazole presented the worst binding affinity, this drug is currently used in Chagas’ disease treatment and was included as negative control. These results together with previous data on the trypanocidal effect of the HIV PIs support the hypothesis that a T. cruzi aspartyl peptidase can be the intracellular target of these inhibitors. However, the direct demonstration of the inhibition of T. cruzi aspartyl peptidase activity by HIV PIs is still a goal to be persuaded. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13104-018-3927-z) contains supplementary material, which is available to authorized users. BioMed Central 2018-11-21 /pmc/articles/PMC6249910/ /pubmed/30463602 http://dx.doi.org/10.1186/s13104-018-3927-z Text en © The Author(s) 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Note
Castilho, Vanessa V. S.
Gonçalves, Keyla C. S.
Rebello, Karina M.
Baptista, Luiz P. R.
Sangenito, Leandro S.
Santos, Helena L. C.
Branquinha, Marta H.
Santos, André L. S.
Menna-Barreto, Rubem F. S.
Guimarães, Ana C.
d’Avila-Levy, Claudia M.
Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase
title Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase
title_full Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase
title_fullStr Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase
title_full_unstemmed Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase
title_short Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase
title_sort docking simulation between hiv peptidase inhibitors and trypanosoma cruzi aspartyl peptidase
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249910/
https://www.ncbi.nlm.nih.gov/pubmed/30463602
http://dx.doi.org/10.1186/s13104-018-3927-z
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