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Avaliação in silico do potencial inibitório de terpenos de Ricinus communis L. sobre a MPro de SARS-CoV-2

Thu, 13 Mar 2025 00:00:00 GMT

Título: Avaliação in silico do potencial inibitório de terpenos de Ricinus communis L. sobre a MPro de SARS-CoV-2 Autor(es): Rocha, Thereza Christina Teixeira Primeiro Orientador: Fernandez, Luzimar Gonzaga Abstract: The SARS-CoV-2 virus, which causes COVID-19, is responsible for a highly contagious disease that can result in severe symptoms in humans. Various strategies have been proposed to combat COVID-19, with one promising approach being the inhibition of the main protease known as MPro (3CLpro). This protease plays a crucial role in viral replication and is both highly conserved and specific among coronaviruses, making it a key target for developing effective inhibitors. Ricinus communis L., commonly known as the castor bean plant, is an oil-rich species that belongs to the Euphorbiaceae family. It has diverse applications in both medical and industrial fields, highlighting its significant socioeconomic value in Brazil. To explore bioactive compounds derived from Brazil's native biodiversity for potential COVID-19 treatments, this study investigated the interactions between 34 terpenes from R. communis and MPro using an in silico methodology that combines Docking and Molecular Dynamics (MD) simulations. Docking analyses were conducted at the active site of MPro and were validated through redocking, cross-docking, correlations with biological activity, and decoys. These analyses were performed using software tools such as AutoDock 4.2, AutoDock Vina, DockThor, and GOLD, utilizing scoring functions like PLP, Goldscore, Chemscore, and ASP to elucidate the primary interactions between the R. communis terpenes and MPro. Based on the Lipinski Rule (Ro5) and efficiency metrics (LE, LLE, and FQ) calculated for each terpene, the five highest-ranked compounds- camphor, 1,8-cineole, α-thujone, ficusic acid, and 6α-hydroxy-10β-methoxy-7α,8α-epoxy-5-oxocasban-20-10-olide- were selected for subsequent MD studies. Following MD analyses, it was determined that among the selected terpenes, ficusic acid (LLE = 3.54, molecular mass = 196 g/mol, RMSD = 3.50 Å) and 6α-hydroxy-10β-methoxy-7α,8α-epoxy-5-oxocasban-20-10-olide (LLE = 3.50, molecular mass = 376 g/mol, RMSD = 9.94 Å) demonstrated noteworthy inhibitory potential against SARS-CoV-2 MPro. Notably, the interactions of these compounds with MPro have not been reported in the literature before, emphasizing their novelty. These findings highlight ficusic acid and 6α-hydroxy-10β-methoxy-7α,8α-epoxy-5-oxocasban-20-10-olide as promising candidates for future in vitro and in vivo studies aimed to treat COVID-19. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação

Perfil transcriptômico dinâmico do leite materno maduro e os impactos bioquímicos no desenvolvimento infantil: uma análise in sílico

Tue, 11 Mar 2025 00:00:00 GMT

Título: Perfil transcriptômico dinâmico do leite materno maduro e os impactos bioquímicos no desenvolvimento infantil: uma análise in sílico Autor(es): Nobrega, Alessandra Santana Primeiro Orientador: Macambira, Simone Garcia Abstract: INTRODUCTION: Breast milk is a mammary glands product of high complexity and specificity, that has a direct impact on the development of human beings. However, despite its significant role, there is still limited information available, especially when it comes to mature milk where little has been discussed about its composition over the years. Among various components present in milk, emerging studies demonstrate that the presence of RNAs in milk is a key component to be evaluated. Therefore, this study performed an analysis based on available public databases of the RNA present in mature milk samples at different periods of time, to define its profile and its variations over time. The hypothesis is that mature breast milk has specific potentialities, according to the degree of maturation that justifies continued breastfeeding. METHODOLOGY: Public transcriptome data from GEODATASET, with accession codes GSE192543 and GSE75726, were analyzed. Available samples were examined using bioinformatics tools through the Galaxy platform. Subsequently, filtering was performed based on the ratio between expression level by Log Fold Change and the p-value <0.05, to identify differentially expressed RNAs between the mature breast milk samples of 01, 02, 04 and 06 months. RESULTS: After data processing, it was possible to find a dynamic gene regulation of the transcripts: being negative in the first months, but positive from the sixth month of lactation; indicating that mature milk is heterogeneous. The presence of these genes, proteins, enzymes and cellular elements in mature breast milk allows the promotion of additional support to the neural, metabolic and immunological development of the still immature infant organism; and elucidates the correlational statistics of health and disease states with the positive practice of breastfeeding. CONCLUSIONS: The components found in mature breast milk samples change to support the diverse biological needs of the infant, providing a responsive cellular environment of increasing complexity. Further studies are necessary to continue the analysis of maternal milk dynamics and its properties after 6 months so that we can establish its long-term behavior. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação

Contribuição da família preniltransferase na aquisição de tolerância a estresses abióticos em Ricinus communis: caracterização in sílico, aspectos evolutivos e expressão gênica

Wed, 25 Sep 2024 00:00:00 GMT

Título: Contribuição da família preniltransferase na aquisição de tolerância a estresses abióticos em Ricinus communis: caracterização in sílico, aspectos evolutivos e expressão gênica Autor(es): Benedicto, Nara Emília Santos Primeiro Orientador: Jesus, Paulo Roberto Ribeiro de Abstract: Ricinus communis L. (castor bean) is a plant with high potential for oil production, widely used in the ricinoleic industry. In Brazil, the Northeast region has the largest cultivation area for this plant, where adverse environmental conditions such as salinity, high temperatures, and drought pose significant challenges to production. Considering the economic and industrial importance of this crop, it is essential to develop strategies to ensure its cultivation under challenging environments. The prenyltransferase (PT) gene family plays a crucial role in encoding enzymes that catalyze the formation of terpenoid skeletons from the intermediates dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP) and transfer prenyl groups to other molecules. These terpenoids generate a wide range of primary and secondary metabolites that are vital for plant responses to environmental stresses. The present study aimed to conduct an in silico analysis of the prenyltransferase protein and gene family in R. communis using bioinformatics tools, seeking to correlate this family with responses to environmental stresses through gene expression, as well as to investigate evolutionary aspects. Similarity searches in the R. communis genome were performed to identify PT proteins, in addition to phylogenetic analyses, subcellular localization predictions, conserved domain and motif identification, gene promoter region analyses, chromosomal mapping, and microarray analyses. A total of 36 PT candidate sequences were identified in R. communis, classified into five distinct subgroups: UbiA, terpene cyclases, prenyltransferase proteins, trans-prenyltransferases, and cis-prenyltransferases. Additionally, conserved domains were identified, such as Z-polyprenyl synthase, polyprenyl synthetase, prenyltransferase subunit alpha repeat, terpene cyclases, squalene-hopene cyclase N-terminal domain, squalene-hopene cyclase C-terminal domain, and the UbiA prenyltransferase superfamily, all associated with prenyltransferases. Cis-prenyltransferases were identified as the oldest PT group. Some proteins showed differential gene expression in response to thermal and saline stresses at different developmental stages.The results of this study provide a deeper understanding of PT proteins in R. communis, establishing a foundation for future research on this gene family in the species. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação

Potencial antioxidante de microalgas marinhas cultivadas sob estresse acídico

Wed, 28 Aug 2024 00:00:00 GMT

Título: Potencial antioxidante de microalgas marinhas cultivadas sob estresse acídico Autor(es): Andrade, Fabrine Souza de Primeiro Orientador: Lima, Suzana Telles da Cunha Abstract: The growing interest in microalgae is due to their photosynthetic characteristics and broad global distribution, making them promise for the production of bioactive compounds with high biological and biotechnological value, applicable in various fields. By modifying the cultivation conditions of these organisms, the production of these compounds can be altered, potentially increasing their efficacy and potential. This study aimed to evaluate the antioxidant activity, phytochemical profile, and phenolic compounds of the microalgae Pyramimonas virginica and Tetraselmis gracilis in response to pH variations (3.0 and 5.0). Antioxidant activity was measured by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging method, while phenol content was determined by the Folin-Ciocalteu method. Toxicity was assessed using Artemia salina, and the phytochemical profile of ethanolic extracts was obtained through qualitative screening. The results showed that microalgae growth was similar for both species; however, those cultivated at pH 3.0 exhibited a significant decrease in optical density, indicating reduced biomass production, leading up to cell death. At pH 5.0, both species showed an increase in optical density comparable to the control (pH 7.0). P. virginica presented a higher yield (0.984 g∙L⁻¹) compared to T. gracilis (0.482 g∙L⁻¹), while the yields for the control were 1.102 g∙L⁻¹ and 1.065 g∙L⁻¹, respectively. In the ethanolic extracts, the antioxidant inhibitory concentration needed to reduce the initial DPPH concentration by 50% (IC50) for P. virginica increased approximately fourfold at pH 5.0 (17.09 mg∙mL⁻¹) compared to the control sample (4.52 mg∙mL⁻¹). For T. gracilis, the IC50 was slightly reduced from 16.7 mg∙mL⁻¹ in the control to 12.57 mg∙mL⁻¹ under acidic cultivation, indicating higher antioxidant activity in this sample. The qualitative phytochemical screening revealed the presence of flavonoids in both species and polyphenols in T. gracilis. Regarding phenolic compounds, P. virginica had the highest content at neutral pH (11.10 ± 0.032 mg GAE/g of extract), while T. gracilis showed an increase in phenolic compound concentration at acidic pH (7.36 ± 0.012 mg GAE/g of extract), corroborating the observed antioxidant activity. In the toxicity test, the ethanolic extracts were not considered toxic to A. salina. These results indicate that the production of bioactive compounds in microalgae can be significantly modulated by cultivation conditions, such as pH, reflecting low toxicity and increased antioxidant potential under low pH conditions. Editora / Evento / Instituição: Universidade Federal da Bahia Tipo: Dissertação