{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T15:17:36Z","timestamp":1790522256425,"version":"4.1.0"},"reference-count":57,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004681","name":"Higher Education Commission, Pakistan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004681","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Moraxella catarrhalis (M<\/jats:italic>.<jats:italic>catarrhalis<\/jats:italic>) is a gram-negative bacterium, responsible for major respiratory tract and middle ear infection in infants and adults. The recent emergence of the antibiotic resistance<jats:italic>M<\/jats:italic>.<jats:italic>catarrhalis<\/jats:italic>demands the prioritization of an effective drug target as a top priority. Fortunately, the failure of new drugs and host toxicity associated with traditional drug development approaches can be avoided by using an<jats:italic>in silico<\/jats:italic>subtractive genomics approach. In the current study, the advanced<jats:italic>in silico<\/jats:italic>genome subtraction approach was applied to identify potential and pathogen-specific drug targets against<jats:italic>M<\/jats:italic>.<jats:italic>catarrhalis<\/jats:italic>. We applied a series of subtraction methods from the whole genome of pathogen based on certain steps i.e. paralogous protein that have extensive homology with humans, essential, drug like, non-virulent, and resistant proteins. Only 38 potent drug targets were identified in this study. Eventually, one protein was identified as a potential new drug target and forwarded to the structure-based studies i.e. histidine kinase (UniProt ID: D5VAF6). Furthermore, virtual screening of 2000 compounds from the ZINC database was performed against the histidine kinase that resulted in the shortlisting of three compounds as the potential therapeutic candidates based on their binding energies and the properties exhibited using ADMET analysis. The identified protein gives a platform for the discovery of a lead drug candidate that may inhibit it and may help to eradicate the otitis media caused by drug-resistant<jats:italic>M<\/jats:italic>.<jats:italic>catarrhalis<\/jats:italic>. Nevertheless, the current study helped in creating a pipeline for drug target identification that may assist wet-lab research in the future.<\/jats:p>","DOI":"10.1371\/journal.pone.0273252","type":"journal-article","created":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T17:50:14Z","timestamp":1661449814000},"page":"e0273252","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Subtractive genomics profiling for potential drug targets identification against Moraxella catarrhalis"],"prefix":"10.1371","volume":"17","author":[{"given":"Bilal","family":"Ashraf","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nimrah","family":"Atiq","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanwal","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdul","family":"Wadood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-4482","authenticated-orcid":true,"given":"Reaz","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"issue":"1","key":"pone.0273252.ref001","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1128\/CMR.15.1.125-144.2002","article-title":"Moraxella catarrhalis: from emerging to established pathogen","volume":"15","author":"C.M. 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Johnson","year":"2008","journal-title":"Nucleic Acids Res."},{"issue":"3","key":"pone.0273252.ref023","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/nar\/gkq784","article-title":"Investigating the predictability of essential genes across distantly related organisms using an integrative approach","volume":"39","author":"J. Deng","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"pone.0273252.ref024","doi-asserted-by":"crossref","first-page":"104608","DOI":"10.1016\/j.micpath.2020.104608","article-title":"Identification of novel non-homologous drug targets against Acinetobacter baumannii using subtractive genomics and comparative metabolic pathway analysis","volume":"152","author":"H. Kaur","year":"2021","journal-title":"Microb. Pathog."},{"issue":"13","key":"pone.0273252.ref025","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1093\/bioinformatics\/btq249","article-title":"PSORTb 3.0: improved protein subcellular localization prediction with refined localization subcategories and predictive capabilities for all prokaryotes.","volume":"26","author":"N.Y. Yu","year":"2010","journal-title":"J. Bioinform"},{"issue":"6","key":"pone.0273252.ref026","doi-asserted-by":"crossref","first-page":"e99368","DOI":"10.1371\/journal.pone.0099368","article-title":"CELLO2GO: a web server for protein subCELlular LOcalization prediction with functional gene ontology annotation","volume":"9","author":"C.-S. Yu","year":"2014","journal-title":"PloS one"},{"issue":"W1","key":"pone.0273252.ref027","doi-asserted-by":"crossref","first-page":"W296","DOI":"10.1093\/nar\/gky427","article-title":"SWISS-MODEL: homology modelling of protein structures and complexes","volume":"46","author":"A. Waterhouse","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"pone.0273252.ref028","doi-asserted-by":"crossref","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK\u2014a program to check the stereochemical quality of protein structures.","volume":"26","author":"R. Laskowski","year":"1993","journal-title":"J. App. Cryst."},{"key":"pone.0273252.ref029","first-page":"678","article-title":"ERRAT","author":"O. Dym","year":"2012","journal-title":"Int. J. Biol."},{"issue":"W1","key":"pone.0273252.ref030","doi-asserted-by":"crossref","first-page":"W402","DOI":"10.1093\/nar\/gkz297","article-title":"The PSIPRED protein analysis workbench: 20 years on","volume":"47","author":"D.W. Buchan","year":"2019","journal-title":"Nucleic Acids Res."},{"issue":"suppl_2","key":"pone.0273252.ref031","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"M. Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"pone.0273252.ref032","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.jgeb.2018.06.006","article-title":"In silico structural homology modeling of nif A protein of rhizobial strains in selective legume plants","volume":"16","author":"S.D. Satyanarayana","year":"2018","journal-title":"J. Genet. Eng. Biotechnol."},{"issue":"2","key":"pone.0273252.ref033","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"O. Trott","year":"2010","journal-title":"J. Comput. Chem."},{"issue":"4","key":"pone.0273252.ref034","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1111\/cbdd.12697","article-title":"A new, improved hybrid scoring function for molecular docking and scoring based on AutoDock and AutoDock Vina","volume":"87","author":"V.Y. Tanchuk","year":"2016","journal-title":"Chem. Biol. Drug Des."},{"key":"pone.0273252.ref035","article-title":"Comparative Metabolic Pathways Analysis and Subtractive Genomics Profiling to Prioritize Potential Drug Targets Against Streptococcus pneumoniae.","volume":"12","author":"K. Khan","year":"2021","journal-title":"Front. Microbiol."},{"key":"pone.0273252.ref036","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.compbiolchem.2019.01.011","article-title":"Identification of glucosyl-3-phosphoglycerate phosphatase as a novel drug target against resistant strain of Mycobacterium tuberculosis (XDR1219) by using comparative metabolic pathway approach","volume":"79","author":"R. Uddin","year":"2019","journal-title":"Comput. Biol. Chem."},{"issue":"1","key":"pone.0273252.ref037","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1021\/ci049714+","article-title":"ZINC\u2212 a free database of commercially available compounds for virtual screening","volume":"45","author":"J.J. Irwin","year":"2005","journal-title":"J. Chem. Inf. Model."},{"issue":"8","key":"pone.0273252.ref038","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1021\/acs.jcim.8b00312","article-title":"Evaluation of AutoDock and AutoDock Vina on the CASF-2013 benchmark","volume":"58","author":"T. Gaillard","year":"2018","journal-title":"J. Chem. Inf. Model."},{"key":"pone.0273252.ref039","first-page":"92037","article-title":"Using AutoDock 4 and AutoDock vina with AutoDockTools: a tutorial","volume":"10550","author":"R. Huey","year":"2012","journal-title":"The Scripps Research Institute Molecular Graphics Laboratory"},{"issue":"18","key":"pone.0273252.ref040","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.2174\/156802608786786624","article-title":"Medicinal chemistry and the molecular operating environment (MOE): application of QSAR and molecular docking to drug discovery.","volume":"8","author":"S. Vilar","year":"2008","journal-title":"Curr. Top. Med. Chem."},{"issue":"9","key":"pone.0273252.ref041","doi-asserted-by":"crossref","first-page":"4066","DOI":"10.1021\/acs.jmedchem.5b00104","article-title":"pkCSM: predicting small-molecule pharmacokinetic and toxicity properties using graph-based signatures","volume":"58","author":"D.E. Pires","year":"2015","journal-title":"J. Med. Chem."},{"issue":"1","key":"pone.0273252.ref042","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep42717","article-title":"SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"A. Daina","year":"2017","journal-title":"Sci. Rep."},{"key":"pone.0273252.ref043","first-page":"132244","article-title":"In Silico Study to Identify New Monoamine Oxidase Type A (MAO-A) Selective Inhibitors from Natural Source by Virtual Screening and Molecular Dynamics Simulation.","author":"K. Jalal","year":"2021","journal-title":"J. Mol. Struct."},{"issue":"D1","key":"pone.0273252.ref044","doi-asserted-by":"crossref","first-page":"D447","DOI":"10.1093\/nar\/gku1003","article-title":"STRING v10: protein\u2013protein interaction networks, integrated over the tree of life","volume":"43","author":"D. Szklarczyk","year":"2015","journal-title":"Nucleic Acids Res."},{"issue":"1","key":"pone.0273252.ref045","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s12539-014-0188-y","article-title":"Application of a subtractive genomics approach for in silico identification and characterization of novel drug targets in Mycobacterium tuberculosis F11.","volume":"6","author":"M.I. Hosen","year":"2014","journal-title":"Interdiscip. Sci"},{"issue":"D1","key":"pone.0273252.ref046","doi-asserted-by":"crossref","first-page":"D605","DOI":"10.1093\/nar\/gkaa1074","article-title":"The STRING database in 2021: customizable protein\u2013protein networks, and functional characterization of user-uploaded gene\/measurement sets","volume":"49","author":"D. Szklarczyk","year":"2021","journal-title":"Nucleic Acids Res."},{"issue":"46","key":"pone.0273252.ref047","doi-asserted-by":"crossref","first-page":"465701","DOI":"10.1088\/0957-4484\/22\/46\/465701","article-title":"Graphene oxide\/ferrofluid\/cement composites for electromagnetic interference shielding application.","volume":"22","author":"A.P. Singh","year":"2011","journal-title":"Nanotechnology"},{"issue":"11","key":"pone.0273252.ref048","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1002\/pro.3705","article-title":"Signal transduction in photoreceptor histidine kinases","volume":"28","author":"A. M\u00f6glich","year":"2019","journal-title":"Protein Sci."},{"issue":"1","key":"pone.0273252.ref049","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/nar\/gkg095","article-title":"The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003","volume":"31","author":"B. Boeckmann","year":"2003","journal-title":"Nucleic Acids Res."},{"issue":"5","key":"pone.0273252.ref050","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1007\/s00044-017-1822-0","article-title":"Structural and functional characterization of a unique hypothetical protein (WP_003901628. 1) of Mycobacterium tuberculosis: a computational approach","volume":"26","author":"R. Uddin","year":"2017","journal-title":"Med. Chem. Res."},{"issue":"11","key":"pone.0273252.ref051","first-page":"1281","article-title":"Proteome-wide subtractive approach to prioritize a hypothetical protein of XDR-Mycobacterium tuberculosis as potential drug target","volume":"41","author":"R. Uddin","year":"2019","journal-title":"Chem. Biol. Drug Des."},{"issue":"11","key":"pone.0273252.ref052","first-page":"1422","article-title":"Comparative Proteome Analysis of Mycobacterium Tuberculosis Strains-H37Ra, H37Rv, CCDC5180, and CAS\/NITR204: A Step Forward to Identify Novel Drug Targets. Lett","volume":"17","author":"S.R. Gupta","year":"2020","journal-title":"Drug Des. Discov."},{"issue":"12","key":"pone.0273252.ref053","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.7164\/antibiotics.56.1045","article-title":"Isolation and characterization of inhibitors of the essential histidine kinase, YycG in Bacillus subtilis and Staphylococcus aureus","volume":"56","author":"T. Watanabe","year":"2003","journal-title":"J. Antibiot."},{"key":"pone.0273252.ref054","doi-asserted-by":"crossref","DOI":"10.1155\/2017\/3783714","article-title":"Application of the subtractive genomics and molecular docking analysis for the identification of novel putative drug targets against Salmonella enterica subsp. enterica serovar Poona","volume":"2017","author":"T. Hossain","year":"2017","journal-title":"Biomed Res. Int."},{"issue":"5","key":"pone.0273252.ref055","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1007\/s12010-012-9620-0","article-title":"Subtractive Genomics Approach to Identify Putative Drug Targets and Identification of Drug-like Molecules for Beta Subunit of DNA Polymerase III in Streptococcus Species","volume":"167","author":"J.J. Georrge","year":"2012","journal-title":"Applied Biochemistry and Biotechnology"},{"issue":"4","key":"pone.0273252.ref056","doi-asserted-by":"crossref","first-page":"1440","DOI":"10.1002\/med.21651","article-title":"Synthesis of histidine kinase inhibitors and their biological properties.","volume":"40","author":"M. Rosales\u2010Hurtado","year":"2020","journal-title":"Med. Res. Rev."},{"issue":"1","key":"pone.0273252.ref057","doi-asserted-by":"crossref","first-page":"132","DOI":"10.3390\/vaccines8010132","article-title":"Development of next generation Streptococcus pneumoniae vaccines conferring broad protection","volume":"8","author":"M. 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