a6a53f231b455da551ad7c1bbfa17d08 pmc_11084791.pdf 340c3ca9e027bcf2a94602da6c13cc3c17a08797 pmc_11084791.pdf fbdd3d4457ffaabd6d35da1695b7c09c4d8c15f02ef4b90656d14aecddb793eb pmc_11084791.pdf Title: Exploring the Antiviral Potential of Natural Compounds against Influenza: A Combined Computational and Experimental Approach Subject: The influenza A virus nonstructural protein 1 (NS1), which is crucial for viral replication and immune evasion, has been identified as a significant drug target with substantial potential to contribute to the fight against influenza. The emergence of drug-resistant influenza A virus strains highlights the urgent need for novel therapeutics. This study proposes a combined theoretical criterion for the virtual screening of molecular libraries to identify candidate NS1 inhibitors. By applying the criterion to the ZINC Natural Product database, followed by ligand-based virtual screening and molecular docking, we proposed the most promising candidate as a potential NS1 inhibitor. Subsequently, the selected natural compound was experimentally evaluated, revealing measurable virus replication inhibition activity in cell culture. This approach offers a promising avenue for developing novel anti-influenza agents targeting the NS1 protein. Keywords: antiviral; natural compounds; influenza; drug resistance; virtual screening Author: Vladimir Perovic, Kristina Stevanovic, Natalya Bukreyeva, Slobodan Paessler, Junki Maruyama, Sergi López-Serrano, Ayub Darji, Milan Sencanski, Draginja Radosevic, Simone Berardozzi, Bruno Botta, Mattia Mori and Sanja Glisic Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25 CreationDate: Sat May 4 03:36:26 2024 CEST ModDate: Sat May 4 03:45:13 2024 CEST Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2971701 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- SOZKOC+VnURWPalladioL-Bold Type 1 Custom yes yes yes 10 0 LRHSYW+URWPalladioL-Bold Type 1 Custom yes yes yes 16 0 TYJUVE+URWPalladioL-Roma Type 1 Custom yes yes yes 22 0 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Date: 2025-02-27 02:10:25 CET RepresentationInformation: pmc_11084791.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-02-27 02:03:37 CET Size: 2971701 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 612 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Results Destination: section.2 Children: Item: Title: The Principal Component Analysis (PCA) Model Destination: subsection.2.1 Item: Title: Molecular Docking Destination: subsection.2.2 Item: Title: The Absorption, Distribution, Metabolism, Elimination, and Toxicity (ADMET) Prediction Destination: subsection.2.3 Item: Title: In Vitro Efficacy Testing of 3-(1H-Indol-3-yl)-N-(4-phenylbutan-2-yl)propanamide against H1N1 and H3N2 Influenza A Viruses Destination: subsection.2.4 Item: Title: Discussion Destination: section.3 Item: Title: Materials and Methods Destination: section.4 Children: Item: Title: Data Preparation Destination: subsection.4.1 Item: Title: EIIP/AQVN Filter Destination: subsection.4.2 Item: Title: PCA Model Destination: subsection.4.3 Item: Title: Molecular Docking Destination: subsection.4.4 Item: Title: ADMET Prediction Destination: subsection.4.5 Item: Title: In Vitro Efficacy Testing against H1N1 and H3N2 Influenza A Viruses Destination: subsection.4.6 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: appendix.A. Info: Title: Exploring the Antiviral Potential of Natural Compounds against Influenza: A Combined Computational and Experimental Approach Author: Vladimir Perovic, Kristina Stevanovic, Natalya Bukreyeva, Slobodan Paessler, Junki Maruyama, Sergi López-Serrano, Ayub Darji, Milan Sencanski, Draginja Radosevic, Simone Berardozzi, Bruno Botta, Mattia Mori and Sanja Glisic Subject: The influenza A virus nonstructural protein 1 (NS1), which is crucial for viral replication and immune evasion, has been identified as a significant drug target with substantial potential to contribute to the fight against influenza. The emergence of drug-resistant influenza A virus strains highlights the urgent need for novel therapeutics. This study proposes a combined theoretical criterion for the virtual screening of molecular libraries to identify candidate NS1 inhibitors. By applying the criterion to the ZINC Natural Product database, followed by ligand-based virtual screening and molecular docking, we proposed the most promising candidate as a potential NS1 inhibitor. Subsequently, the selected natural compound was experimentally evaluated, revealing measurable virus replication inhibition activity in cell culture. This approach offers a promising avenue for developing novel anti-influenza agents targeting the NS1 protein. 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