Biology subjects

de Lima Neto, D. F.

Publications and source records attributed to de Lima Neto, D. F..

6 recordsLinked to original sources

bioRxiv2026

Pressure-cooling remodeling of TMV coat protein reveals mechanically partitioned capsid dynamics and selective epitope masking

High hydrostatic pressure (HHP) perturbs protein assemblies by shifting conformational equilibria toward lower-volume states and by reorganizing hydration at cavities, interfaces, and solvent-exposed surfaces (Heremans 1982; Akasaka 2006; Roche et al. 2012; Hata, Nishiyama, and Kitao 2020). Here, we integrate pressure-dependent molecular dynamics descriptors, pressure-temperature interpretation, structure-based epitope prediction, and face-resolved intersubunit metrics to examine how pressure and pressure-cooling treatment remodel the tobacco mosaic virus coat protein (TMVcp) assembly. The pressure response is not adequately explained as uniform shrinkage. Instead, the data support a hierarchical transition from a broad, native-like conformational ensemble at low pressure, through a cooperative compacting regime around 1000- 1750 bar, toward a high-pressure compact state with reduced configurational diversity, suppressed global mobility, and localized residual fragility. A representative TMVcp face composed of A2, A3, A4, A19, A20, A21, A35, A36, and A37 behaves as a mechanically partitioned network: A3 behaves as a principal deformation hub, A20-A21-A35-A37 forms a lateral/diagonal compression corridor, A21 behaves as a bridge node, A36 acts as an anisotropic relay, and A2, A4, and A19 behave as stabilizing or adaptive anchors. Pairwise minimum-distance profiles, per-subunit radius of gyration, and post-fit RMSD converge around a late trajectory interval near 358-365 ns, suggesting a coordinated face-level breathing event rather than independent stochastic noise. These local dynamics provide a conservative structural explanation for predicted pressure-dependent epitope remodeling: HHP may mask canonical solvent-exposed epitopes by reducing loop mobility and closing intersubunit grooves, whereas pressure followed by low-temperature trapping may selectively preserve only protrusions compatible with the compact, hydration-trapped lattice. Because DiscoTope and ElliPro are computational predictors, these results should be interpreted as structural hypotheses requiring experimental validation by antibody binding assays, mutagenesis, HDX-MS, or high-pressure structural approaches.

microbiology↗

bioRxiv2026

Integrative Genomic and Structure-Based Prioritization of Molecular Targets in Multidrug-Resistant Salmonella enterica from Brazilian Poultry

Salmonella spp. remains one of the leading foodborne pathogens worldwide, and the circulation of multidrug-resistant strains in the poultry industry poses a significant challenge. In this study, five isolates from poultry litter swabs (commercial broiler chickens) belonging to the Salmonella Heidelberg and Salmonella Minnesota serovars were characterized using an integrated approach involving phenotypic resistance profiling, whole-genome sequencing, structural prioritization of molecular targets, and in silico screening of ligands. All isolates exhibited multidrug resistance phenotypes and genetic repertoires consistent with resistance to {beta}-lactams, sulfonamides, and tetracyclines, as well as determinants linked to efflux systems, virulence, and persistence. Genomic analysis allowed for the prioritization of five proteins for structural investigation: CTX-M-2, CMY-2, Sul2, AcrB, and SpvC. Sequence-structure validation revealed high correspondence between the proteins of the isolates and the experimental structures selected for CMY-2, Sul2, AcrB, and SpvC, while CTX-M-2 was modeled with high structural confidence. Molecular docking analyses with GNINA revealed distinct behaviors among the targets. Sul2 showed biological relevance but a more conservative structural response, with no significant gain after analog generation. In contrast, AcrB stood out as the most promising target, with analogs generated by BRICS yielding better scores and, in some cases, coherent international networks identified by PLIP. The results demonstrate that the integration of phenotype, comparative genomics, and structural prioritization constitutes a rational strategy for selecting targets and molecular candidates in multidrug-resistant avian strains of S. Heidelberg and S. Minnesota.

microbiology↗

bioRxiv2026

An Open-Source Reproducible Workflow for Pocket-Oriented Virtual Screening and ADME-Integrated Chemoinformatics: A Multi-Target Flavivirus Case Study

Zika virus (ZIKV), yellow fever virus (YFV), West Nile virus (WNV), Usutu virus (USUV), and Saint Louis encephalitis virus (SLEV) remain major public health concerns, yet broad-spectrum antiviral options are limited. Here, we present an open-source, reproducible software workflow for pocket-oriented virtual screening and ADME-integrated chemoinformatics, designed to support standardized multi-target compound prioritization. As a case study, the workflow was applied to structural and nonstructural proteins from clinically relevant flaviviruses. Automated pocket detection using Concavity reduces site-selection bias by generating docking boxes from surface concavity clusters, while standardized downstream scripts parse docking logs, convert docking-derived binding energies into Kd-related metrics, integrate SwissADME descriptors, and compute LE, LLE, FQ, and drug-likeness rules. The framework also supports retrospective validation and comparative benchmarking using literature-supported reference compounds and target-specific plausibility checks. Rather than proposing experimentally validated antiviral candidates, this study provides a reusable computational framework for hypothesis generation, benchmarking, and downstream experimental prioritization in structure-based drug discovery. The workflow is modular and adaptable to other multi-target screening campaigns where integrated ranking across binding, physicochemical, and ADME dimensions is required. SUMMARYWe describe an open-source, reproducible software workflow that integrates pocket-oriented docking, ligand efficiency scoring, ADME descriptor integration, and multivariate chemoinformatics to standardize compound prioritization across multiple protein targets. The workflow combines open-source tools with auditable Bash, R, and Python scripts and is demonstrated through a multi-target flavivirus case study. Rather than claiming experimentally validated antiviral activity, the framework is intended to support hypothesis generation, retrospective benchmarking, transparent reporting, and downstream experimental prioritization.

bioinformatics↗

bioRxiv2025

Integrative Proteome-Wide Structural Analysis and High-Throughput Docking Identify Broad-Spectrum Antiviral Scaffolds Against Zika, Yellow Fever, West Nile, Saint Louis Encephalitis, and Usutu Viruses

Integrative proteome-wide virtual screening offers a powerful route to discover broad-spectrum antivirals against emerging flaviviruses, for which no approved therapeutics currently exist. Here, we address this gap by constructing homology models of all structural and nonstructural proteins from Zika, Yellow Fever, West Nile, Saint Louis Encephalitis, and Usutu viruses. We applied a standardized pipeline--combining sequence and structure based pocket prediction (Concavity), electrostatic profiling (APBS), and pharmacokinetic filtering (Lipinskis rules, ADMET)--to generate high-confidence binding sites. A focused library of 160 natural product scaffolds and repurposed antivirals was then docked exhaustively (2,000 runs per pocket) using AutoDock4/Vina, followed by clustering and ranking by binding energy. Comparative analyses (RMSD, PCA, RMSF) confirmed conserved core folds alongside virus-specific surface signatures, guiding grid definition. Of the 45 top-ranked scaffolds, several flavonoids exhibited dual-site binding to the NS5 polymerase and E glycoprotein across [≥]4 viruses, while ribavirin and sofosbuvir engaged conserved catalytic motifs in NS3/NS5, highlighting opportunities for combination strategies. Lead compounds such as myricetin (Kd {approx} 1.9 {micro}M), temoporfin (Kd {approx} 1.2 nM), and aurintricarboxylic acid (Kd {approx} 1.9 {micro}M) demonstrated favorable multitarget profiles. This integrative framework prioritizes robust candidates for experimental validation and optimization of panflaviviral therapeutics.

microbiology↗

bioRxiv2018

Porcine Parvovirus VP1/VP2 on a Time Series Epitope Mapping: exploring the effects of high hydrostatic pressure on the immune recognition of antigens.

Porcine parvovirus (PPV) is a DNA virus that causes reproductive failure in gilts and sows, resulting in embryonic and fetal losses worldwide. Epitope mapping of PPV is important for developing new vaccines. In this study, we used spot synthesis analysis for epitope mapping of the capsid proteins of PPV (NADL-2 strain) and correlated the findings with predictive data from immunoinformatics. The virus was exposed to three conditions prior to inoculation in pigs: native (untreated), high hydrostatic pressure (350 MPa for 1 h) at room temperature and high hydrostatic pressure (350 MPa for 1h) at -18 {degrees}C, compared with a commercial vaccine produced using inactivated PPV. The screening of serum samples detected 44 positive spots corresponding to 20 antigenic sites. Each type of inoculated antigen elicited a distinct epitope set. In silico prediction located linear and discontinuous epitopes in B cells that coincided with several epitopes detected in spot synthesis of sera from pigs that received different preparations of inoculum. The approach used here provided important information on the antibody/antigen interactions required to improve B cell responses to PPV and may be useful in developing novel strategies for producing new vaccines.\n\nAbbreviations3D, three dimensional; HHP, high hydrostatic pressure; ID, identification; IEDB, Immune Epitope Database; ORFs, open reading frames; p.i., post-infection; PPV, porcine parvovirus; RMSD, root-mean-square deviation of atomic positions; R(g), radius of gyration. RMSF, root-mean-square fluctuation; SK6, Swine kidney cell; SPF, specific pathogen free; TCID50/mL, Median Tissue Culture Infectious Dose; HI, Hemagglutination Inhibition.

microbiology↗

bioRxiv2018

Molecular dynamics suggests antiviral compounds active against Dengue Virus show similar binding patterns to Zika Virus proteins

The Zika virus (ZIKV) arrival in Brazilian territory brought to light the need for preparedness regarding arboviruses in Brazil. Compound screening is a cumbersome process dependent upon in vitro testing and validation. Recently, virtual screening methods have improved precision and reliability providing a framework for in silico testing of lead compound candidates. Here we have applied these methods on compounds that were previously shown to be active against Dengue virus in vitro, taking the structural information of such compounds and applying docking methods to identify putative binding sites. A molecular dynamics approach was also used to refine the docking results. The computational experiments ran here suggests that compounds such as Epigallocatechin Gallate, Ergotamine and Avermectin-B1a bind to active sites on the viral enzymes NS5 and NS3, as well as on its Envelope protein. Refinement shows that such bindings were not lost during the production run and key regions on both enzymes were structurally displaced on average over the simulation time. Interestingly there is no documented drug interactions among these candidates, raising the possibility of drug combinations during treatments. Moreover, the candidate compounds have been extensively studied, thus providing important information regarding intracellular interactions caused by them, which are also associated with pathways exploited by the virus, suggesting possible side interactions hindering the replication process.

microbiology↗