PGBIOTECM https://repositorio.ufpb.br/jspui/handle/tede/338 2026-10-31T14:33:45Z 2026-10-31T14:33:45Z Vasconcelos, Izabelle Salviano de https://repositorio.ufpb.br/jspui/handle/123456789/39559 2026-10-10T06:10:30Z 2026-03-26T00:00:00Z

Título: Busca farmacofórica baseada em grupos químicos identifica moléculas promissoras contra as proteínas do SARS-CoV-2 Autor(es): Vasconcelos, Izabelle Salviano de Orientador: Folador, Edson Luiz Abstract: The SARS-CoV-2 pandemic highlighted the need for new therapeutic strategies, especially in the face of the emergence of variants with greater transmissibility and immune escape. In this context, virtual screening emerges as a promising in silico strategy for computer-aided drug discovery. Among the promising natural products in the development of new drugs, rutin stands out, studied for its pharmacological properties and antiviral activity. In this context, the present work aimed to perform a pharmacophore search, using chemical groups generated with rutin analogs as a model, aiming to identify molecules capable of inhibiting SARS- CoV-2 proteins. Initially, 220 molecules with structural similarity to rutin were downloaded from the PubChem database. For target selection, 4,124 three-dimensional structures of SARS-CoV-2 proteins were selected from the Protein Data Bank (PDB) and filtered by structural similarity, retaining those with RMSD >0.5 angstroms, resulting in 1,569 3D structures. From these structures, 193,561 pockets were predicted, with 4,000 retained having a druggability score ≥ 0.5. The 4,000 pockets and 220 selected ligands were prepared and subjected to docking, totaling 346,952 complexes generated by QuickVina 2, accounting for more than 3 million interactions with PLIP, generating 1,268 chemical groups, which were used for pharmacophore search. The pharmacophore search was performed using Pharmit in 10 databases, using the following filters: molecular weight range between 300 and 600, logP and number of rotatable bonds between 3 and 6, number of acceptor hydrogens from 4 to 12 and donor hydrogens from 0 to 6. This screening resulted in 174,359 molecules that were subjected to energy minimization and subsequent pharmacokinetic profile evaluation using ADMET-AI, observing that 67,912 molecules stood out with favorable ADMET profiles, presenting a better pharmacokinetic profile when compared to emergency drugs. Among the best molecules, 15 stood out for their superior affinity, ADMET, and toxicological safety parameters, interacting at the 8SDG-pocket 66, 8FEZ-pocket 228, 8H3E-pocket 2, 8H3E- pocket 3, and 8DRU-pocket 1 binding sites with the best ΔG (between -11 and -14.1 kcal/mol). Interaction characterization analysis demonstrated that the highlighted molecules exhibit amino acid residue interaction patterns similar to those described in the literature, suggesting a possible inhibitory effect against SARS-CoV-2. These findings highlight the relevance of these compounds as potential therapeutic candidates and are suggested for future in vivo and in vitro analyses. Furthermore, the results corroborate the potential of the hybrid virtual screening approach in the search for promising candidates for therapy against SARS- CoV-2. Editor: Universidade Federal da Paraíba Tipo: Dissertação

2026-03-26T00:00:00Z Goncalves, Rayra Mirella Rodrigues https://repositorio.ufpb.br/jspui/handle/123456789/39311 2026-09-29T06:11:18Z 2026-03-25T00:00:00Z

Título: Busca farmacofórica baseada em grupos químicos identifica moléculas que sugerem atividade contra proteínas de Mycobacterium tuberculosis Autor(es): Goncalves, Rayra Mirella Rodrigues Orientador: Folador, Edson Luiz Abstract: Tuberculosis remains one of the leading causes of death from infectious diseases worldwide, further aggravated by the emergence of multidrug-resistant strains of Mycobacterium tuberculosis and by the therapeutic limitations of currently available drugs. In this context, the present study aimed to perform a pharmacophore-based search to identify molecules with potential activity against M. tuberculosis proteins through an integrated computational approach combining ligand-based virtual screening (LBVS), structure-based virtual screening (SBVS), molecular docking, protein–ligand interaction analysis, and in sílico pharmacokinetic evaluation. Initially, 228 analogs of first-line anti-tuberculosis drugs were identified in the PubChem database. In parallel, 3,246 protein structures were retrieved from the Protein Data Bank and subsequently refined after exclusion based on structural similarity. Cavity analysis using fpocket resulted in 4,081 pockets with a druggability score ≥ 0.5, which were subjected to molecular docking with the selected analogs, totaling 63,219 evaluated complexes. Interaction characterization using PLIP enabled the identification of relevant chemical groups, which were employed to construct pharmacophore models applied in the PHARMIT platform, leading to the screening of 117,198 molecules. ADMET evaluation demonstrated that a significant portion of the compounds exhibited pharmacokinetic profiles predictively superior to those of reference drugs. Among the best-ranked complexes were proteins involved in essential metabolic pathways, such as thymidylate kinase, enoyl-ACP reductase, and anthranilate phosphoribosyltransferase. In addition, interactions not previously described in the literature suggest that the screened ligands may explore alternative regions of active sites, expanding the possibilities for the rational design of innovative inhibitors. The incorporation of druggability criteria, Lipinski’s rules, and ADMET analysis allowed refinement of compounds with greater potential for progression within the drug development pipeline. The results indicate that the integrated strategy employed is effective in identifying promising candidates, providing a rational basis for future experimental validation and contributing to the development of new therapeutic alternatives against tuberculosis. Editor: Universidade Federal da Paraíba Tipo: Dissertação

2026-03-25T00:00:00Z Nascimento, Marta Maria Amâncio do https://repositorio.ufpb.br/jspui/handle/123456789/38275 2026-07-06T06:12:24Z 2014-11-12T00:00:00Z

Título: Bactérias endofíticas na produção de biomassa e potencial teórico de etanol do sorgo sacarino (Sorghum bicolor, L.) em condições de estresse salino Autor(es): Nascimento, Marta Maria Amâncio do Orientador: Salinas, Cosme Rafael Martinez Abstract: The sweet sorghum is an alternative for the production of ethanol and biomass in areas that have water deficit, and/or salinity that restrict agricultural activity for showing tolerance to these abiotic stresses. Endophytic bacteria have been indicated as a factor of production in various cultures to confer nutritional, hormonal advantages, among others that result in promoting growth of plants (PGPB). Objective of this work is to evaluate the potential of endophytic bacteria as a factor of production of sorghum under saline and non- saline conditions. An experimental model was established in the laboratory to select cultivars of sorghum and sorghum PGPB with stress and without salt stress. Cultivars were selected from 13 genotypes (Sorghum bicolor: Rio, BR 501, BR 506, Roma, Ramada, Tale, Theis, Willey, Wray, IPA 467-4-2, SF-15, IPA 8602502 and, S. sudanense: Sudan- 4202) cultured (30 d) in nutrient solution containing 8 and 75 mM NaCl. Three cultivars were tolerant (IPA 8602502, Rio, Tale and BR 501) and two susceptible (Ramada and Wray). The Wray cv. was used for selecting PGPB (isolated from sugarcane). The IPACC8, IPACC9 (Herbaspirillum seropedicae) and IPACC12 (Azoarcus sp.) isolates were selected and evaluated with reference strains (BR11192 and BR11175). The three isolates attenuate the effect of salinity on water consumption of Wray. Without salt stress, some endophytes promoted biomass production in shoots (BR11192) or root (IPACC12 and IPACC8). The IPACC12 induced more hydrated plants. Endophytes were field tested with Wray and IPA 467-4-2 cultivars grown in saline and non saline soils. The fertilization with N (+N) or without N (-N) were controls. Juice production in +N, IPACC9 and IPACC12, promoted the highest theoretical ethanol (>14.9 m3 ∙ha-1 ) achieved in -N (9.7 m3 ∙ha-1 ) and, TEP promoted by IPACC12 was higher (1703 L∙ha-1 ) than –N (908 L∙ha-1 ), however, the TEP was intermediate in the other treatments (±1259 L∙ha-1 ) in non-saline soils. In saline soil, BR11175 showed higher biomass yield (28.8 Mg∙ha-1 ) than –N (20.9 Mg∙ha-1 ), however, not differ to +N (±25.36 Mg∙ha-1 ). Juice yields and TEP, treatments did not differ (±9.03 m3 ∙ha-1 and ±830.2 L∙ha-1 ). Adaptability analysis of PGPB effect over soil conditions showed stable effects on juice production and TEP. IPACC12 promotes the production of juice and TEP in sweet sorghum at least equivalent to N fertilization over soil condition. Editor: Universidade Federal da Paraíba Tipo: Tese

2014-11-12T00:00:00Z Nascimento, Carlos Vinícius Carvalho do https://repositorio.ufpb.br/jspui/handle/123456789/38274 2026-07-06T06:12:18Z 2019-02-27T00:00:00Z

Título: Bactérias diazotróficas endofíticas na cultura do sorgo sacarino [Sorghum bicolor (L.) Moench]: estratégias de isolamento, promoção do crescimento e mitigação de estresses de salinidade e nitrogênio Autor(es): Nascimento, Carlos Vinícius Carvalho do Orientador: Salinas, Cosme Rafael Martínez Abstract: Diazotrophic bacteria convert atmospheric N2 into ammonia through biological fixation, presenting other attributes related to plant growth promoting (PGP), such as indoleacetic acid production (IAA), phosphate solubilization, 1-aminocyclopropane-1-carboxylate activity (ACC), which contribute to the attenuation of environmental stresses. Therefore, they serve as a promising, sustainable, and low-cost alternative for the increase of plant productivity and expansion of sorghum (Sorghum bicolor) in the Northeast, Brazil. In the first stage, the PGP activity and abiotic stress attenuation in sorghum were evaluated by isolates of Achromobacter xylosoxidans and Enterobacter bugandensis, from sugarcane stalks in the Zona da Mata of the state of Paraíba. Simple inocula were effective (Duncan's test; p≤0.05) under nitrogen stress condition (2 mM). Co-inoculation were not more effective than simple inoculums under N stress, however, they presented a PGP competence under double stress condition (2 mM N + 75 mM NaCl). In the second stage, were isolated and characterized 103 new diazotrophs (from stem and leaves) of three sorghum cultivars (BRS 506; IPA 467-4-2; SF-15) in three regions (Zona da Mata, Agreste, Sertão) in the state of Pernambuco, using five isolation media (JNFb; NFb; LGI; LGI-P; JMV). Fourteen species were obtained, belonging to the genera Pseudomonas (16 isolates), Pantoea (54), Agrobacterium (9), Sphingomonas (12), Herbaspirillum (10), Acinetobacter (1) and Serratia (1), being Pantoea the most widespread. Non-metric multidimensional scaling showed that region was the most important factor (PERMANOVA: p=0.004) shaping the diazotrophic communities. The Sertão communities presented lower structural diversity, with predominance of Pantoea. In the Zona da Mata and Agreste communities, Pseudomonas, Pantoea and Agrobacterium predominated. Although a conserved core has been observed for the production of IAA and halotolerance, Dunn's test (p≤0.05) showed that: a) Sertão communities present high IAA productions (~3.11 μM·h-1 ) and are predominantly halotolerant and halophytic, whereas communities Zona da Mata and Agreste were specialized in the metabolization of ACC; b) JMV and LGI-P media accessed communities with, respectively, high production of IAA (3.04 μM·h-1 ) and phosphate solubilization (IS = 2.96); c) communities of BRS 506 cultivar were superior in the production of IAA (2.68 μM·h-1 ) and solubilization of phosphate (IS = 2.14), being predominantly halotolerant and halophytes. Spearman’s correlations indicated parameters related to soil salinity (exchangeable Na+ and K + , CEC, S value, PES, EC) that influence the abundance of some species. In the third stage, PGP sorghum trials (cv. Wray) showed that isolates from Sertão and Agreste were more promising, which induced greater efficiency of vegetal water consumption. Increased root (BR; 85.8%) and shoot (BS; 38.6%) biomass production in the condition of simple stress (3 mM N) were induced by Agrobacterium pusense ICS2 and TCI2, respectively. In the condition of double stress (3 mM N + 75 mM NaCl), the highest production in BR (108.1%) and BS (75.4%) were induced by Pseudomonas oryzihabitans CFS2 and Pantoea stewartii subsp. indologenes TFB1. The results indicate that the use of JMV and LGI-P for isolation, BRS 506 as a host plant, can be a good alternative for the access of putative endophytes from Sertão soils with high PGP potential, particularly for sorghum. Editor: Universidade Federal da Paraíba Tipo: Tese

2019-02-27T00:00:00Z