Bioinformatics Guided Identification of Key genes and Docking-Supported SAR and QSAR Analysis of Cathepsin S (CTSS) Inhibitors Relevant to Acute Respiratory Distress Syndrome

Bioinformatics Guided Identification of Key genes and Docking-Supported SAR and QSAR Analysis of Cathepsin S (CTSS) Inhibitors Relevant to Acute Respiratory Distress Syndrome | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Bioinformatics Guided Identification of Key genes and Docking-Supported SAR and QSAR Analysis of Cathepsin S (CTSS) Inhibitors Relevant to Acute Respiratory Distress Syndrome Basavaraj Vastrad, Shivaling Pattanashetti, Chanabasayya Vastrad This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8461507/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Acute respiratory distress syndrome (ARDS) is the most widespread pathological change in diseases of the respiratory system. However, we know poorly about the molecular mechanisms and effective therapeutic approaches of ARDS. The ARDS RNA- sequencing dataset, GSE279069, was downloaded from the Gene Expression Omnibus (GEO) database. Using the DESeq2 package of r bioconductor to screen Differentially expressed genes (DEGs). Gene ontology (GO) and REACTOME pathway enrichment analysis were performed on the DEGs. Meanwhile, using the HiPPIE database and Cytoscape software to construct protein-protein interaction (PPI) network and modules. The hub gene-related miRNA-hub gene regulatory network, TF-hub gene regulatory network were constructed. Next, DrugBank database was utilized to search for alternative drugs targeting ARD hub genes. Diagnostic values of hub genes were assessed by receiver operating characteristic (ROC) curves analysis. Finally, molecular docking and QSAR analysis were performed to validate the interaction between 1q and 1r, and the hub gene Cathepsin S. 958 DEGs (479 up-regulated and 479 down-regulated) were identified from 135 ARDS patients and 74 normal control samples. These DEGs were found to be enriched for various gene ontology (GO) functions and pathways, including response to stimulus, membrane, hydrolase activity, multicellular organismal process, cell periphery, transporter activity, immune system and neuronal system. A protein-protein interaction (PPI) network was established using these 958 genes. The top hub genes (FN1, ARRB1, ENG, HTRA4, ATM, HTR2C, ELAVL2, FGB, APLNR and SIGLECL1) were acquired through calculation by the Network Analyzer plug-in in Cytoscape software. Key miRNAs (hsa-miR-30d-5p and hsa-miR-28-5p), TFs (NR0B1 and PHOX2B) and drug molecules (Zenarestat and Chlorpromazine) were predicted. Molecular docking analysis revealed that compound 1q and 1r binds to Cathepsin S with a binding energy of -7.8 kcal/mol, indicating highly stable binding. In summary, the DEGs and hub genes identified in the present investigation not only contribute to a better understanding of the molecular mechanisms underlying the progression of ARDA, but might also serve as potential new biomarkers and targets for ARDA. Bioinformatics Computational Biology Drug Discovery, Design, & Development Acute respiratory distress syndrome bioinformatics analysis biomarkers hub genes differentially expressed genes Molecular docking QSAR Full Text Additional Declarations The authors declare no competing interests. Tables are available in the Supplementary Files section. Supplementary Files TablesF.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8461507","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":566189017,"identity":"27fb62f6-bf0e-45c7-8f60-4dd3f52de663","order_by":0,"name":"Basavaraj Vastrad","email":"","orcid":"https://orcid.org/0000-0003-2202-7637","institution":"Department of Pharmaceutical Chemistry, K.L.E. 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