Biology subjects

Soares, A. P.

Publications and source records attributed to Soares, A. P..

3 recordsLinked to original sources

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

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↗