دورية أكاديمية
Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase.
| العنوان: | Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase. |
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| المؤلفون: | Castilho VVS; Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Gonçalves KCS; Laboratório de Estudos Integrados em Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Rebello KM; Laboratório de Estudos Integrados em Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Baptista LPR; Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Sangenito LS; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Santos HLC; Laboratório de Estudos Integrados em Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Branquinha MH; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Santos ALS; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes (LEAMER), Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Menna-Barreto RFS; Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., Guimarães AC; Laboratório de Genômica Funcional e Bioinformática, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil., d'Avila-Levy CM; Laboratório de Estudos Integrados em Protozoologia, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil. davila.levy@ioc.fiocurz.br.; de Duve Institute, Université Catholique de Louvain, Brussels, Belgium. davila.levy@ioc.fiocurz.br. |
| المصدر: | BMC research notes [BMC Res Notes] 2018 Nov 21; Vol. 11 (1), pp. 825. Date of Electronic Publication: 2018 Nov 21. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Biomed Central Country of Publication: England NLM ID: 101462768 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-0500 (Electronic) Linking ISSN: 17560500 NLM ISO Abbreviation: BMC Res Notes Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Biomed Central, 2008. |
| مواضيع طبية MeSH: | Drug Repositioning* , Molecular Docking Simulation*, Anti-HIV Agents/*pharmacology , Aspartic Acid Proteases/*chemistry , Peptide Hydrolases/*chemistry , Protease Inhibitors/*pharmacology , Trypanosoma cruzi/*enzymology, Atazanavir Sulfate/pharmacology ; Crystallography, X-Ray ; Databases, Protein ; HIV/drug effects ; Nelfinavir/pharmacology ; Protein Conformation ; Saccharomyces cerevisiae Proteins/chemistry ; Saquinavir/pharmacology |
| مستخلص: | 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. |
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| معلومات مُعتمدة: | 001 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BR); x Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (BR); x Fundação Oswaldo Cruz (BR); x Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR) |
| فهرسة مساهمة: | Keywords: Aspartic peptidase; Chagas’ disease; Chemotherapy; Drug-repurposing; Neglected tropical diseases |
| المشرفين على المادة: | 0 (Anti-HIV Agents) 0 (DDI1 protein, S cerevisiae) 0 (Protease Inhibitors) 0 (Saccharomyces cerevisiae Proteins) 4MT4VIE29P (Atazanavir Sulfate) EC 3.4.- (Aspartic Acid Proteases) EC 3.4.- (Peptide Hydrolases) HO3OGH5D7I (Nelfinavir) L3JE09KZ2F (Saquinavir) |
| تواريخ الأحداث: | Date Created: 20181123 Date Completed: 20190408 Latest Revision: 20190408 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC6249910 |
| DOI: | 10.1186/s13104-018-3927-z |
| PMID: | 30463602 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1756-0500 |
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| DOI: | 10.1186/s13104-018-3927-z |