Effective natural inhibitors targeting granzyme B in rheumatoid arthritis by computational study.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36582296", "kind": "science-record", "revision": 4, "content_hash": "sha256:1ae129a61862f4b095776d93919bd7df2c25bad2151133889e54f5c475697ecd", "created_at": "2026-11-01T19:01:08Z", "updated_at": "2026-11-01T22:50:58Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Effective natural inhibitors targeting granzyme B in rheumatoid arthritis by computational study.", "doi": "10.3389/fmed.2022.1052792", "pmid": "36582296", "authors": ["Xinyu Wang", "Ye Jiang", "Pengcheng Zhou", "Liangxin Lin", "Yilin Yang", "Qifan Yang", "Jiting Zhang", "Dong Zhu"], "journal": "Frontiers in medicine", "year": 2022, "abstract": "Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, and current treatments for RA fall short of the outcomes expected by clinicians and patients.\nObjectives: This study aimed to identify novel therapeutic and prognostic targets in RA at the genomic level and to screen desirable compounds with potential inhibitory effects on GZMB.\nMethods: We performed differential gene analysis on GSE55235 and GSE55457 from Gene Expression Omnibus (GEO) and then obtained the intersection of the two differentially expressed genes (DEGs) lists by drawing Venn diagrams. Then we performed protein-protein interaction (PPI) network analysis, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis on the DEGs of the intersection. Next, we downloaded the crystal structure of Granzyme B (GZMB). Molecular docking technology was used to screen potential inhibitors of GZMB in subsequent experiments, and we then analyzed the toxicity and water solubility of these potential inhibitors for future drug experiments. Finally, whether the docking of these small molecules with GZMB is stable is tested by molecular dynamics.\nResults: A total of 352 mutual DEGs were identified. Twenty hub genes were obtained according to PPI network analysis, among which the GZMB gene attracted the attention of our research. Three potent natural compounds, ZINC000004557101, ZINC000012495776, and ZINC000038143593, bound to GZMB, show better binding affinity. Furthermore, they are predicted to own low Ames mutagenicity, developmental toxicity potential, rodent carcinogenicity, and high tolerance to cytochrome P4502D6. Molecular dynamics simulations show that ZINC000004557101 and GZMB have more advantageous potential energy and can exist stably in a natural environment. Moreover, we finally verified the inhibitory effect of ZINC000004557101 on granzyme B by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western blotting experiment.\nConclusion: RA patients showed increased GZMB expression. ZINC000004557101 is a potential drug targeting GZMB for treating RA.", "claims": [{"id": "claim-method", "statement": "The limma package was used to identify DEGs based on comparing expression values between standard and RA samples (20).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36582296", "locator": "sections[14] \"Identification of differentially expressed genes\" paragraph 2", "quote": "The limma package was used to identify DEGs based on comparing expression values between standard and RA samples (20)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36582296", "locator": "sections[25] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "By performing Venn diagram analysis (Figures 2E–G), 352 mutual DEGs were identified in these two datasets, including 258 upregulated and 91 downregulated genes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36582296", "locator": "sections[3] \"Identification of differentially expressed genes\" paragraph 2", "quote": "By performing Venn diagram analysis (Figures 2E–G), 352 mutual DEGs were identified in these two datasets, including 258 upregulated and 91 downregulated genes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "By performing Venn diagram analysis (Figures 2E–G), 352 mutual DEGs were identified in these two datasets, including 258 upregulated and 91 downregulated genes.", "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:36582296"], "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:GSE55235"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "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:GSE55235"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36582296", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmed.2022.1052792", "sha256": "sha256:a9d9c0d2b758df1aabd41a85499fff26d8a570e0ae9f007a56b5b49ec45b3f2d", "bytes": 41864, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmed.2022.1052792", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9792495", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE55235", "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=GSE55235", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55235", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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