Neuropilin-1: A Conserved Entry Receptor for SARS-CoV-2 and a Potential Therapeutic Target.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40722799", "kind": "science-record", "revision": 3, "content_hash": "sha256:b0cb529b6f3097390e9eec14964adaa5a4a894bb19a7adce25e6bddb2511dcbc", "created_at": "2026-11-01T20:30:49Z", "updated_at": "2026-11-01T22:14:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Neuropilin-1: A Conserved Entry Receptor for SARS-CoV-2 and a Potential Therapeutic Target.", "doi": "10.3390/biomedicines13071730", "pmid": "40722799", "authors": ["Vivany Maydel Sierra-Sánchez", "Citlali Margarita Blancas-Napoles", "Aina Daniela Sánchez-Maldonado", "Indira Medina", "Rodrigo Romero-Nava", "Fengyang Huang", "Enrique Hong", "Asdrúbal Aguilera-Méndez", "Sergio Adrian Ocampo-Ortega", "Santiago Villafaña"], "journal": "Biomedicines", "year": 2025, "abstract": "Background/Objectives: Neuropilin-1 (NRP1) is a key co-receptor for SARS-CoV-2, complementing the ACE2 receptor. Several investigations have documented highly conserved sequences in this receptor, supporting the implication of NRP1 as a key mediator in SARS-CoV-2 cellular entry mechanisms. Methods: To investigate this hypothesis, we examined 104,737 SARS-CoV-2 genome fastas from GISAID genomic data, corresponding to isolates collected between 2020 and 2025 in Mexico. Specifically, we focused on the RRAR motif, a known furin-binding site for NRP-1 and the binding site for ACE2 with the spike protein. Our analysis revealed high conservation (>98%) of the RRAR domain compared to a rapidly diminishing ACE2-binding domain. A complementary analysis, using Data from Gene Expression Omnibus (GEO, GSE150316), showed that NRP1 expression in lung tissue remains relatively stable, whereas ACE2 displayed high inter-individual variability and lower abundance compared to NRP1. Based on this evidence, we designed two humans-rats NRP1 siRNAs that were tested in vivo using a melittin-induced lung injury model. Results: The RT-PCR assays confirmed an effective NRP1 knockdown, and the siRNA-treated group showed a significant reduction in the lesions severity. These findings highlight NRP1 as a stable and relevant therapeutic target and suggest the protective potential of siRNA-mediated gene silencing. Conclusions: The evidence presented here supports the rational design of NRP1-directed therapies for multiple circulating SARS-CoV-2 variants in Mexico.", "claims": [{"id": "claim-method", "statement": "In addition, paired Wilcoxon signed-rank tests were conducted to compare the expression levels of NRP1 and ACE2 within the same samples, stratified by group (control or COVID-19).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40722799", "locator": "sections[10] \"2.8. Statistical Analysis\" paragraph 2", "quote": "In addition, paired Wilcoxon signed-rank tests were conducted to compare the expression levels of NRP1 and ACE2 within the same samples, stratified by group (control or COVID-19)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original data used and analyzed in this study are available in public databases. SARS-CoV-2 sequences were obtained from GISAID (https://www.gisaid.org/). Gene expression data were obtained from the GEO repository under accession number GSE150316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150316 (accessed on 4 July 2025)). Additionally, COVID-19 data from the Mexican national CONACYT repository (https://datos.covid-19.conacyt.mx/#DownZCSV (accessed on 4 July 2025)) were used. All additional data generated or analyzed during this study are included in this published article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40722799", "locator": "sections[25] \"Data Availability Statement\" paragraph 2", "quote": "The original data used and analyzed in this study are available in public databases. SARS-CoV-2 sequences were obtained from GISAID (https://www.gisaid.org/). Gene expression data were obtained from the GEO repository under accession number GSE150316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150316 (accessed on 4 July 2025)). Additionally, COVID-19 data from the Mexican national CONACYT repository (https://datos.covid-19.conacyt.mx/#DownZCSV (accessed on 4 July 2025)) were used. All additional data generated or analyzed during this study are included in this published article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The NRP1-targeting siRNAs significantly reduced NRP1 expression in both lungs and significantly reduced melittin-induced lung injury compared with melittin alone.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "This difference was statistically significant (p < 0.05)."}, "evidence": [{"asset": "source:pmid:40722799", "locator": "sections[19] \"3.6. Evaluation of the Effect of siRNA Administration in a Melittin-Induced Lung Injury Model\" paragraph 4", "quote": "The administered siRNAs exerted a protective effect on lung tissue, as the extent of injury following melittin administration was significantly lower in the siRNA-treated groups compared to the control group."}, {"asset": "source:pmid:40722799", "locator": "sections[19] \"3.6. Evaluation of the Effect of siRNA Administration in a Melittin-Induced Lung Injury Model\" paragraph 5", "quote": "This difference was statistically significant (p < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The NRP1-targeting siRNAs significantly reduced NRP1 expression in both lungs and significantly reduced melittin-induced lung injury compared with melittin alone.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40722799"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE150316"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE150316"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40722799", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/biomedicines13071730", "sha256": "sha256:0d7a8084f32dad7c6ae23121a1d4223c025fe8c361d01ad417abe350c970bca2", "bytes": 57801, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/biomedicines13071730", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12292943", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE150316", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150316", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE150316", "version": null, "note": "The original data used and analyzed in this study are available in public databases. SARS-CoV-2 sequences were obtained from GISAID (https://www.gisaid.org/). Gene expression data were obtained from the GEO repository under accession number GSE150316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150316 (accessed on 4 July 2025)). Additionally, COVID-19 data from the Mexican national CONACYT repository (https://datos.covid-19.conacyt.mx/#DownZCSV (accessed on 4 July 2025)) were used. All additional data generated or analyzed during this study are included in this published article.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original data used and analyzed in this study are available in public databases. SARS-CoV-2 sequences were obtained from GISAID (https://www.gisaid.org/). Gene expression data were obtained from the GEO repository under accession number GSE150316 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE150316 (accessed on 4 July 2025)). Additionally, COVID-19 data from the Mexican national CONACYT repository (https://datos.covid-19.conacyt.mx/#DownZCSV (accessed on 4 July 2025)) were used. 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