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Vieira de Sa, R.

Publications and source records attributed to Vieira de Sa, R..

3 recordsLinked to original sources

CBM KG: A Comorbidity-Centric Knowledge Graph Uncovering Causal Pathomechanisms Between COVID-19 and Neurodegenerative Diseases

SummaryCOVID-19 is increasingly recognized as a potential trigger or accelerator of neurodegenerative diseases such as Alzheimers and Parkinsons. To systematically explore the putative molecular and clinical associations between them, we present CBM KG (Causal Biological Mechanisms Knowledge Graph)--a manually curated, comorbidity-centric resource developed within the EU-funded COMMUTE project. CBM KG integrates over 2,800 cause-and-effect or correlative relationships from 63 peer-reviewed publications, highlighting key mechanisms such as viral entry routes, blood-brain barrier alteration, microglial activation, neuroinflammation, and APOE {varepsilon}4-associated susceptibility. Each relationship in the graph is fully traceable to its source evidence, ensuring transparency and reproducibility. Unlike general-purpose or single disease-focused knowledge graphs, CBM KG is specifically designed to represent causal biological mechanisms spanning both infectious and neurodegenerative processes. By encoding directional, cause-and-effect relationships, it supports the interpretation of clinical co-occurrences through plausible mechanistic links between overlapping disease pathways, offering high-resolution insights at both molecular and clinical levels. Availability and implementationThe BEL files, Neo4j database, and Cytoscape visualization files are publicly available at: https://github.com/SCAI-BIO/CBM-Comorbidity-KG.

bioinformatics↗

Parechovirus-3 infection disrupts immunometabolism and leads to glutamate excitotoxicity in neural organoids

Parechovirus ahumpari 3 (HPeV-3), is among the main agents causing severe neonatal neurological infections such as encephalitis and meningitis. However, the underlying molecular mechanisms and changes to the host cellular landscape leading to neurological disease has been understudied. Through quantitative proteomic analysis of HPeV-3 infected neural organoids, we identified unique metabolic changes following HPeV-3 infection that indicate immunometabolic dysregulation. Protein and pathway analyses showed significant alterations in neurotransmission and potentially, neuronal excitotoxicity. Elevated levels of extracellular glutamate, lactate dehydrogenase (LDH), and neurofilament light (NfL) confirmed glutamate excitotoxicity to be a key mechanism contributing to neuronal toxicity in HPeV-3 infection and can lead to apoptosis induced by caspase signaling. These insights are pivotal in delineating the metabolic landscape following severe HPeV-3 CNS infection and may identify potential host targets for therapeutic interventions.

neuroscience↗

Assessment of The Broad-Spectrum Host Targeting Antiviral Efficacy of Halofuginone Hydrobromide in Human Airway, Intestinal and Brain Organoid Models.

Halofuginone hydrobromide has shown potent antiviral efficacy against a variety of viruses such as SARS-CoV-2, dengue, or chikungunya virus, and has, therefore, been hypothesized to have broad-spectrum antiviral activity. In this paper, we tested this broad-spectrum antiviral activity of Halofuginone hydrobomide against viruses from different families (Picornaviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, and Flaviviridae). To this end, we used relevant human models of the airway and intestinal epithelium and regionalised neural organoids. Halofuginone hydrobomide showed antiviral activity against SARS-CoV-2 in the airway epithelium with no toxicity at equivalent concentrations used in human clinical trials but not against any of the other tested viruses. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=199 HEIGHT=200 SRC="FIGDIR/small/565121v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@10d562eorg.highwire.dtl.DTLVardef@94f903org.highwire.dtl.DTLVardef@683b6forg.highwire.dtl.DTLVardef@11620ba_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIHalofuginone hydrobromide was identified as a possible broad-spectrum host targeting antiviral drug. C_LIO_LIHuman organoid models offer a physiologically relevant and clinically translatable model for antiviral research. C_LIO_LIHalofuginone hydrobromide shows antiviral efficacy against SARS-CoV-2, but not against EV-A71, PeV-A1, IAV, RV-A16, HCMV or ZIKV in relevant organoid models. C_LIO_LIThe efficacy of Halofuginone hydrobromide is concentration dependent as well as on proline content of the host receptor(s) or host factors for the specific virus in question. C_LI

microbiology↗