In silico Screening of Plant-Derived Natural Compounds as Potential Inhibitors of DNA Gyrase Subunit A of Escherichia coli

In silico Screening of Plant-Derived Natural Compounds as Potential Inhibitors of DNA Gyrase Subunit A of Escherichia coli | 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 In silico Screening of Plant-Derived Natural Compounds as Potential Inhibitors of DNA Gyrase Subunit A of Escherichia coli Manasa Panduranga This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8620356/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 The rapid emergence of antibiotic-resistant Escherichia coli strains created an urgent need for novel antibacterial agents. DNA gyrase subunit A (GyrA) is an essential drug target enzyme involved in bacterial DNA replication. In the present study, an in silico approach was employed by screening plant-derived natural compounds as potential E. coli GyrA inhibitors. The three-dimensional structure of GyrA was retrieved from the Protein Data Bank and prepared for molecular docking. A total of ten phytochemicals with reported antimicrobial properties were selected and docked against the target protein using AutoDock Vina. The binding affinities and molecular interactions were analyzed to identify lead compounds. Drug-likeness and ADMET properties were calculated using SwissADME and pkCSM tools. Amongst the screened compounds, quercetin, berberine, and luteolin showed strong binding affinities and favorable interaction profiles comparable to standard antibiotics. ADMET analysis has identified acceptable pharmacokinetic properties for the top-scoring compounds. This study infers that the selected natural compounds could be promising lead molecules for developing novel antibacterial agents targeting DNA gyrase A of E. coli. Introduction Antimicrobial resistance has emerged as a significant challenge in the health sector across the globe, with the E. coli bacteria proving to be the most frequent agent associated with infections acquired either in the community or within health institutions. Nonetheless, the intensive use of antibiotics has influenced the development of multiple resistant strains of E. coli, making it less vulnerable to current treatment modalities, thereby creating a great need for new antibacterial agents. DNA gyrase is a type II topoisomerase that is found exclusively in prokaryotes, being an important enzyme involved in the replication, transcription, and segregation of DNA. It is a two-subunit protein, with the A subunit, GyrA, being solely involved in the breaking and resealing of the DNA structure. The subunit A of the protein is a prime target for antibacterial medication as it is nonessential to eukaryotes. Natural compounds derived from plants have traditionally been a good source of bioactive compounds with various biological properties, such as antimicrobial activity. Modern bioinformatics tools and techniques in computational biology have made it possible to conduct screens of such compounds using computer simulations. The objective of this study is to look for possible inhibitors of the E. coli DNA gyrase subunit A using molecular docking techniques of some natural compounds derived from plants. Materials and Methods Retrieval of Target Protein The three-dimensional crystal structure of DNA gyrase subunit A of Escherichia coli was retrieved from PDB. The selected structure was downloaded in PDB format and prepared for docking analysis. Protein Preparation Protein preparation included the removal of the bound waters and co-crystallized ligands. Polar hydrogens were added, as well as the application of Kollman charges using the AutoDock Tools. The protein preparation file was then saved as PDBQT, which is the file type required for the process of molecular docking. Selection of Natural Compounds In this research, ten natural compounds with antibacterial properties isolated from plants were chosen: quercetin, curcumin, berberine, kaempferol, apigenin, luteolin, resveratrol, epigallocatechin gallate, naringenin, and gallic acid. The three-dimensional structures of these compounds were obtained from the PubChem database with the format of SDF. Ligand Preparation PyRx software was used to import the ligands. Energy minimization was conducted on the ligands. The minimized molecules were then saved in the PDBQT format. Molecular Docking Molecular docking was carried out employing AutoDock Vina integrated into PyRx. The grid box was established to encompass the active site of DNA gyrase A. The default parameters of docking were employed. Binding affinities were noted, and docked structures were assessed based on binding affinity. Interaction Analysis The docked protein and ligand structures were modeled with Discovery Studio Visualizer and PyMOL for visualization of hydrogen bonds, hydrophobic forces, and crucial amino acids. Drug-Likeness and ADMET Analysis Drug-like properties of the identified compounds were evaluated employing the SwissADME tool according to Lipinski’s Rule of Five. ADME and Toxicity properties were predicted employing the pkCSM online tool. Results Molecular Docking Analysis Results from molecular docking showed different binding affinities of natural compounds that had been selected towards subunit A of DNA gyrase. Out of those compounds, it was observed that Quercetin had the highest binding affinity towards subunit A of DNA gyrase. Other compounds having higher binding affinity included Berberine and Luteolin. All these compounds demonstrated binding affinity similar to that of standard antibiotics. Interaction Profile By interaction analysis, it was found that the highest ranked compounds had formed stable hydrogen bonds and hydrophobic interactions with the important active-site residues of DNA gyrase A. These are critical for inhibitory activity and indicate the possibility of enzyme inhibition. Drug Likeness/ADMET Results from the analysis by SwissADME also showed that the majority of the selected molecules satisfied Lipinski's Rule of Five, making them have good oral bioavailability. Data from pkCSM analysis also showed that all the highest-scoring molecules exhibited good absorption and had low toxicity. Discussion Moreover, resistance among E. coli strains towards conventional antibiotics has become a justification to investigate alternative treatments. An in-silico modeling study was conducted to search for natural compounds that could bind with DNA gyrase subunit A, one of the most important enzymes that sustain life in bacterial cells. Molecular docking scores identified that some phytochemicals strongly interact with the enzyme. Quercetin, berberine, and luteolin possess a promising inhibitory ability owing to their stable interactions with the crucial residues of the target protein. The desirable ADMET and drug-likeness properties establish its potential to act as a lead compound. However, it is important to validate these results and the antibacterial activity of these compounds through viable experiments and in vivo tests. In silico outcomes are significant and assist in gaining initial insights. Conclusion In the current study, potential natural inhibitors of DNA gyrase subunit A from Escherichia coli have been successfully discovered using the methods of molecular docking and pharmacokinetics. Quercetin, berberine, and luteolin have been recognized as potential lead compounds with high binding affinity, suggesting that natural compounds of plant origin could be successfully applied for developing novel antibacterial agents. Declarations Author Contribution Manasa Panduranga conceived and designed the study, performed literature review, carried out molecular docking and ADMET analysis, interpreted the results, and drafted the original manuscript. All authors have read and approved the final manuscript and agree to be accountable for all aspects of the work. Acknowledgement Authors would also like to thank the Department of Biotechnology,St. Joseph’s College for Women (A), Visakhapatnam, Andhra Pradesh, India, for providing support. Authors would like to thank the free bioinformatics tools which are used in this study. References Bush K, Bradford PA (2020) Epidemiology of β-lactamase-producing pathogens. Clin Microbiol Rev 33(2):e00047–e00019 World Health Organization (2019) Antimicrobial resistance: global report on surveillance. WHO, Geneva Reece RJ, Maxwell A (1991) DNA gyrase: structure and function. Crit Rev Biochem Mol Biol 26(3–4):335–375 Hooper DC, Jacoby GA (2015) Mechanisms of drug resistance: quinolone resistance. Ann N Y Acad Sci 1354(1):12–31 Drlica K, Zhao X (1997) DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61(3):377–392 Collin F, Karkare S, Maxwell A (2011) Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol 92:479–497 Aldred KJ, Kerns RJ, Osheroff N (2014) Mechanism of quinolone action and resistance. Biochemistry 53(10):1565–1574 Maxwell A, Lawson DM (2003) The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Curr Top Med Chem 3(3):283–303 Cowan MM (1999) Plant products as antimicrobial agents. Clin Microbiol Rev 12(4):564–582 Gibbons S (2004) Anti-staphylococcal plant natural products. Nat Prod Rep 21(2):263–277 Daglia M (2012) Polyphenols as antimicrobial agents. Curr Opin Biotechnol 23(2):174–181 Cushnie TPT, Lamb AJ (2005) Antimicrobial activity of flavonoids. Int J Antimicrob Agents 26(5):343–356 Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS et al (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30(16):2785–2791 Trott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking. J Comput Chem 31(2):455–461 Kitchen DB, Decornez H, Furr JR, Bajorath J (2004) Docking and scoring in virtual screening for drug discovery. Nat Rev Drug Discov 3:935–949 Meng XY, Zhang HX, Mezei M, Cui M (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 7(2):146–157 Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H et al (2000) The Protein Data Bank. Nucleic Acids Res 28(1):235–242 Kim S, Chen J, Cheng T, Gindulyte A, He J, He S et al (2021) PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res 49(D1):D1388–D1395 UniProt Consortium (2023) UniProt: the universal protein knowledgebase in 2023. Nucleic Acids Res 51(D1):D523–D531 Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability. Adv Drug Deliv Rev 46(1–3):3–26 Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness. Sci Rep 7:42717 Pires DEV, Blundell TL, Ascher DB (2015) pkCSM: predicting small-molecule pharmacokinetic and toxicity properties. J Med Chem 58(9):4066–4072 Kaper JB, Nataro JP, Mobley HLT (2004) Pathogenic Escherichia coli . Nat Rev Microbiol 2:123–140 Poirel L, Madec JY, Lupo A, Schink AK, Kieffer N, Nordmann P et al (2018) Antimicrobial resistance in Escherichia coli . Clin Microbiol Infect 24(9):915–926 Additional Declarations No competing interests reported. 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-8620356","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":606249654,"identity":"fe32af40-89cf-4e7e-b737-cb435c21703d","order_by":0,"name":"Manasa Panduranga","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBADOftm5oMPgAwePmK1GBuwtyUbgLSwEaslcQPPGTMJEIugFt32swc//qi5w7hdIi2t8muOnQwbA/PDRzfwaDE7k5cszXPsGbPljORjt2W3JQMdxmZsnINPy4EcA2kGtsNsDDfS0m5LbmMGauFhk8ar5fwb458//h3mYbiRY1Ysua2eCC1AlRK8bYclDM6cMWP8uO0wMVremFnz9j0zkGxvS5Zm3Hach42ZkF/O5xjf/PHtTn0/M/PBjz+3Vdvzszc/fIxPCxQcAJPMPGCSsHKEFsYfxKkeBaNgFIyCEQYAHWVLhds2Q1wAAAAASUVORK5CYII=","orcid":"","institution":"St. Joseph’s College for Women(A) Visakhapatnam - Andhra Pradesh","correspondingAuthor":true,"prefix":"","firstName":"Manasa","middleName":"","lastName":"Panduranga","suffix":""}],"badges":[],"createdAt":"2026-01-16 15:08:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8620356/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8620356/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104712160,"identity":"84677639-436f-4a3e-b4f3-9cce7b476e2a","added_by":"auto","created_at":"2026-03-16 10:29:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":245044,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8620356/v1/949d6dd1-f115-4482-9a96-b1ff4dc2501a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"In silico Screening of Plant-Derived Natural Compounds as Potential Inhibitors of DNA Gyrase Subunit A of Escherichia coli","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAntimicrobial resistance has emerged as a significant challenge in the health sector across the globe, with the E. coli bacteria proving to be the most frequent agent associated with infections acquired either in the community or within health institutions. Nonetheless, the intensive use of antibiotics has influenced the development of multiple resistant strains of E. coli, making it less vulnerable to current treatment modalities, thereby creating a great need for new antibacterial agents.\u003c/p\u003e \u003cp\u003eDNA gyrase is a type II topoisomerase that is found exclusively in prokaryotes, being an important enzyme involved in the replication, transcription, and segregation of DNA. It is a two-subunit protein, with the A subunit, GyrA, being solely involved in the breaking and resealing of the DNA structure. The subunit A of the protein is a prime target for antibacterial medication as it is nonessential to eukaryotes.\u003c/p\u003e \u003cp\u003eNatural compounds derived from plants have traditionally been a good source of bioactive compounds with various biological properties, such as antimicrobial activity. Modern bioinformatics tools and techniques in computational biology have made it possible to conduct screens of such compounds using computer simulations. The objective of this study is to look for possible inhibitors of the E. coli DNA gyrase subunit A using molecular docking techniques of some natural compounds derived from plants.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eRetrieval of Target Protein\u003c/p\u003e \u003cp\u003eThe three-dimensional crystal structure of DNA gyrase subunit A of Escherichia coli was retrieved from PDB. The selected structure was downloaded in PDB format and prepared for docking analysis.\u003c/p\u003e \u003cp\u003eProtein Preparation\u003c/p\u003e \u003cp\u003eProtein preparation included the removal of the bound waters and co-crystallized ligands. Polar hydrogens were added, as well as the application of Kollman charges using the AutoDock Tools. The protein preparation file was then saved as PDBQT, which is the file type required for the process of molecular docking.\u003c/p\u003e \u003cp\u003eSelection of Natural Compounds\u003c/p\u003e \u003cp\u003eIn this research, ten natural compounds with antibacterial properties isolated from plants were chosen: quercetin, curcumin, berberine, kaempferol, apigenin, luteolin, resveratrol, epigallocatechin gallate, naringenin, and gallic acid. The three-dimensional structures of these compounds were obtained from the PubChem database with the format of SDF.\u003c/p\u003e \u003cp\u003eLigand Preparation\u003c/p\u003e \u003cp\u003ePyRx software was used to import the ligands. Energy minimization was conducted on the ligands. The minimized molecules were then saved in the PDBQT format.\u003c/p\u003e \u003cp\u003eMolecular Docking\u003c/p\u003e \u003cp\u003eMolecular docking was carried out employing AutoDock Vina integrated into PyRx. The grid box was established to encompass the active site of DNA gyrase A. The default parameters of docking were employed. Binding affinities were noted, and docked structures were assessed based on binding affinity.\u003c/p\u003e \u003cp\u003eInteraction Analysis\u003c/p\u003e \u003cp\u003eThe docked protein and ligand structures were modeled with Discovery Studio Visualizer and PyMOL for visualization of hydrogen bonds, hydrophobic forces, and crucial amino acids.\u003c/p\u003e \u003cp\u003eDrug-Likeness and ADMET Analysis\u003c/p\u003e \u003cp\u003eDrug-like properties of the identified compounds were evaluated employing the SwissADME tool according to Lipinski\u0026rsquo;s Rule of Five. ADME and Toxicity properties were predicted employing the pkCSM online tool.\u003c/p\u003e "},{"header":"Results","content":"\u003cp\u003eMolecular Docking Analysis\u003c/p\u003e \u003cp\u003eResults from molecular docking showed different binding affinities of natural compounds that had been selected towards subunit A of DNA gyrase. Out of those compounds, it was observed that Quercetin had the highest binding affinity towards subunit A of DNA gyrase. Other compounds having higher binding affinity included Berberine and Luteolin. All these compounds demonstrated binding affinity similar to that of standard antibiotics.\u003c/p\u003e \u003cp\u003eInteraction Profile\u003c/p\u003e \u003cp\u003eBy interaction analysis, it was found that the highest ranked compounds had formed stable hydrogen bonds and hydrophobic interactions with the important active-site residues of DNA gyrase A. These are critical for inhibitory activity and indicate the possibility of enzyme inhibition.\u003c/p\u003e \u003cp\u003eDrug Likeness/ADMET\u003c/p\u003e \u003cp\u003eResults from the analysis by SwissADME also showed that the majority of the selected molecules satisfied Lipinski's Rule of Five, making them have good oral bioavailability. Data from pkCSM analysis also showed that all the highest-scoring molecules exhibited good absorption and had low toxicity.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eMoreover, resistance among E. coli strains towards conventional antibiotics has become a justification to investigate alternative treatments. An in-silico modeling study was conducted to search for natural compounds that could bind with DNA gyrase subunit A, one of the most important enzymes that sustain life in bacterial cells. Molecular docking scores identified that some phytochemicals strongly interact with the enzyme.\u003c/p\u003e \u003cp\u003eQuercetin, berberine, and luteolin possess a promising inhibitory ability owing to their stable interactions with the crucial residues of the target protein. The desirable ADMET and drug-likeness properties establish its potential to act as a lead compound. However, it is important to validate these results and the antibacterial activity of these compounds through viable experiments and in vivo tests. In silico outcomes are significant and assist in gaining initial insights.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn the current study, potential natural inhibitors of DNA gyrase subunit A from Escherichia coli have been successfully discovered using the methods of molecular docking and pharmacokinetics. Quercetin, berberine, and luteolin have been recognized as potential lead compounds with high binding affinity, suggesting that natural compounds of plant origin could be successfully applied for developing novel antibacterial agents.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eManasa Panduranga conceived and designed the study, performed literature review, carried out molecular docking and ADMET analysis, interpreted the results, and drafted the original manuscript. All authors have read and approved the final manuscript and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e \u003cp\u003eAuthors would also like to thank the Department of Biotechnology,St. Joseph\u0026rsquo;s College for Women (A), Visakhapatnam, Andhra Pradesh, India, for providing support. Authors would like to thank the free bioinformatics tools which are used in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBush K, Bradford PA (2020) Epidemiology of β-lactamase-producing pathogens. Clin Microbiol Rev 33(2):e00047\u0026ndash;e00019\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWorld Health Organization (2019) Antimicrobial resistance: global report on surveillance. WHO, Geneva\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReece RJ, Maxwell A (1991) DNA gyrase: structure and function. Crit Rev Biochem Mol Biol 26(3\u0026ndash;4):335\u0026ndash;375\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHooper DC, Jacoby GA (2015) Mechanisms of drug resistance: quinolone resistance. Ann N Y Acad Sci 1354(1):12\u0026ndash;31\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDrlica K, Zhao X (1997) DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev 61(3):377\u0026ndash;392\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollin F, Karkare S, Maxwell A (2011) Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol 92:479\u0026ndash;497\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAldred KJ, Kerns RJ, Osheroff N (2014) Mechanism of quinolone action and resistance. Biochemistry 53(10):1565\u0026ndash;1574\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaxwell A, Lawson DM (2003) The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Curr Top Med Chem 3(3):283\u0026ndash;303\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCowan MM (1999) Plant products as antimicrobial agents. Clin Microbiol Rev 12(4):564\u0026ndash;582\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGibbons S (2004) Anti-staphylococcal plant natural products. Nat Prod Rep 21(2):263\u0026ndash;277\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaglia M (2012) Polyphenols as antimicrobial agents. Curr Opin Biotechnol 23(2):174\u0026ndash;181\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCushnie TPT, Lamb AJ (2005) Antimicrobial activity of flavonoids. Int J Antimicrob Agents 26(5):343\u0026ndash;356\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS et al (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30(16):2785\u0026ndash;2791\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTrott O, Olson AJ (2010) AutoDock Vina: improving the speed and accuracy of docking. J Comput Chem 31(2):455\u0026ndash;461\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKitchen DB, Decornez H, Furr JR, Bajorath J (2004) Docking and scoring in virtual screening for drug discovery. Nat Rev Drug Discov 3:935\u0026ndash;949\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng XY, Zhang HX, Mezei M, Cui M (2011) Molecular docking: a powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des 7(2):146\u0026ndash;157\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H et al (2000) The Protein Data Bank. Nucleic Acids Res 28(1):235\u0026ndash;242\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim S, Chen J, Cheng T, Gindulyte A, He J, He S et al (2021) PubChem in 2021: new data content and improved web interfaces. Nucleic Acids Res 49(D1):D1388\u0026ndash;D1395\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUniProt Consortium (2023) UniProt: the universal protein knowledgebase in 2023. Nucleic Acids Res 51(D1):D523\u0026ndash;D531\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability. Adv Drug Deliv Rev 46(1\u0026ndash;3):3\u0026ndash;26\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDaina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness. Sci Rep 7:42717\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePires DEV, Blundell TL, Ascher DB (2015) pkCSM: predicting small-molecule pharmacokinetic and toxicity properties. J Med Chem 58(9):4066\u0026ndash;4072\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaper JB, Nataro JP, Mobley HLT (2004) Pathogenic \u003cem\u003eEscherichia coli\u003c/em\u003e. Nat Rev Microbiol 2:123\u0026ndash;140\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePoirel L, Madec JY, Lupo A, Schink AK, Kieffer N, Nordmann P et al (2018) Antimicrobial resistance in \u003cem\u003eEscherichia coli\u003c/em\u003e. Clin Microbiol Infect 24(9):915\u0026ndash;926\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8620356/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8620356/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe rapid emergence of antibiotic-resistant Escherichia coli strains created an urgent need for novel antibacterial agents. DNA gyrase subunit A (GyrA) is an essential drug target enzyme involved in bacterial DNA replication. In the present study, an in silico approach was employed by screening plant-derived natural compounds as potential E. coli GyrA inhibitors. The three-dimensional structure of GyrA was retrieved from the Protein Data Bank and prepared for molecular docking. A total of ten phytochemicals with reported antimicrobial properties were selected and docked against the target protein using AutoDock Vina. The binding affinities and molecular interactions were analyzed to identify lead compounds. Drug-likeness and ADMET properties were calculated using SwissADME and pkCSM tools. Amongst the screened compounds, quercetin, berberine, and luteolin showed strong binding affinities and favorable interaction profiles comparable to standard antibiotics. ADMET analysis has identified acceptable pharmacokinetic properties for the top-scoring compounds. This study infers that the selected natural compounds could be promising lead molecules for developing novel antibacterial agents targeting DNA gyrase A of E. coli.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e","manuscriptTitle":"In silico Screening of Plant-Derived Natural Compounds as Potential Inhibitors of DNA Gyrase Subunit A of Escherichia coli","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-16 10:28:40","doi":"10.21203/rs.3.rs-8620356/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"17c2189b-eb0b-4960-b186-e4fb9a644b70","owner":[],"postedDate":"March 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-16T10:28:40+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-16 10:28:40","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8620356","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8620356","identity":"rs-8620356","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}