{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T01:40:37Z","timestamp":1787881237958,"version":"build-2784847793"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T00:00:00Z","timestamp":1651622400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004697","name":"Hamadan University of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004697","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["International Journal of Microbiology"],"published-print":{"date-parts":[[2022,5,4]]},"abstract":"<jats:p>Staphylococcus aureus (S. aureus) is responsible for several disorders including skin and soft tissue infections, bacteremia, pulmonary infections, septic arthritis, osteomyelitis, meningitis, gastroenteritis, toxic-shock syndrome, and urinary tract infections. Methicillin-resistant S. aureus (MRSA) contains penicillin-binding protein 2a (SauPBP2a) responsible for catalyzing the peptidoglycan production within the bacterial cell wall. The binding affinity of SauPBP2a to beta-lactam antibiotics is low, and thus, it is necessary to discover new effective SauPBP2a inhibitors to combat mortality and morbidity in patients affected by MRSA. The binding affinity of 46 natural flavonoids to the SauPBP2a active site was examined via molecular docking analysis. The stability of docked poses associated with the top-ranked flavonoids was tested by performing molecular dynamics (MD) in 10 nanoseconds (ns) computer simulations. Kaempferol 3-rutinoside-7-sophoroside and rutin demonstrated a considerable binding affinity to the SauPBP2a active site (\u0394<jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>G<\/a:mi>\n                     <\/a:math>\n                  <\/jats:inline-formula>binding\u2009&lt;\u2009<jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mo>\u2212<\/c:mo>\n                     <\/c:math>\n                  <\/jats:inline-formula>11\u2009kcal\/mol). Their docked poses were found to be stable for 10\u2009ns MD simulations. Kaempferol 3-rutinoside-7-sophoroside and rutin also exhibited salient binding affinity to the enzyme\u2019s allosteric site. This study suggests that kaempferol 3-rutinoside-7-sophoroside and rutin may be considered as drug candidates for therapeutic aims in several human infections associated with MRSA. Nevertheless, in vitro and in vivo confirmations are warranted.<\/jats:p>","DOI":"10.1155\/2022\/9130700","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T23:05:15Z","timestamp":1651705515000},"page":"1-14","source":"Crossref","is-referenced-by-count":38,"title":["Methicillin-Resistant Staphylococcus aureus: Docking-Based Virtual Screening and Molecular Dynamics Simulations to Identify Potential Penicillin-Binding Protein 2a Inhibitors from Natural Flavonoids"],"prefix":"10.1155","volume":"2022","author":[{"given":"Motahareh","family":"Masumi","sequence":"first","affiliation":[{"name":"Students Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Noormohammadi","sequence":"additional","affiliation":[{"name":"Students Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Kianisaba","sequence":"additional","affiliation":[{"name":"Students Research Committee, Hamadan University of Medical Sciences, Hamadan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Nouri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biotechnology, School of Pharmacy, Hamadan University of Medical Sciences, Hamadan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4128-8613","authenticated-orcid":true,"given":"Mohammad","family":"Taheri","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6546-8785","authenticated-orcid":true,"given":"Amir","family":"Taherkhani","sequence":"additional","affiliation":[{"name":"Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2013.08.018"},{"key":"2","first-page":"88","article-title":"Outbreaks of community-associated methicillin-resistant Staphylococcus aureus skin infections\u2013Los Angeles county, California, 2002-2003","volume":"52","author":"CFD Control and Prevention","year":"2003","journal-title":"MMWR: Morbidity and Mortality Weekly Report"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1086\/533590"},{"key":"4","volume-title":"Staphylococcus aureus","author":"T. A. Taylor","year":"2021"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00134-14"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2008.10.003"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1007\/s00203-020-02071-y"},{"key":"8","first-page":"870","article-title":"Structural basis for the \u03b2 lactam resistance of PBP2a from methicillin-resistant Staphylococcus aureus","volume":"9","author":"D. Lim","year":"2002","journal-title":"Nature Structural Biology"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10080934"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2020.104144"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2005.04.014"},{"key":"12","first-page":"1593","article-title":"CpG hypermethylation of collagen type I \u03b1 2 contributes to proliferation and migration activity of human bladder cancer","volume":"34","author":"K. Mori","year":"2009","journal-title":"International Journal of Oncology"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.1186\/s12906-015-0580-0"},{"key":"14","first-page":"24","article-title":"Natural flavonoids as antimicrobial agents","volume":"7","author":"W. Bylka","year":"2004","journal-title":"Jana"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1002\/1099-1573(200102)15:1<39::aid-ptr684>3.0.co;2-r"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5b00056"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1002\/elps.200900140"},{"key":"19","doi-asserted-by":"crossref","first-page":"3664","DOI":"10.1021\/ja500053x","article-title":"Discovery of a new class of non-\u03b2-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity","volume":"136","author":"P. I. O\u2019Daniel","year":"2014","journal-title":"Journal of the American Chemical Society"},{"key":"20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m112.355644"},{"key":"21","doi-asserted-by":"publisher","DOI":"10.1089\/152791602317250351"},{"issue":"14","key":"22","first-page":"1","article-title":"Using autodock for ligand-receptor docking","volume":"24","author":"G. M. Morris","year":"2008","journal-title":"Current Protocols in Bioinformatics"},{"key":"23","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21256"},{"key":"24","doi-asserted-by":"publisher","DOI":"10.1021\/ci500118s"},{"key":"25","doi-asserted-by":"publisher","DOI":"10.1021\/jm051256o"},{"key":"26","article-title":"Computational and in vitro validation of cardiogenic induction of quercetin on adipose-derived mesenchymal stromal cells through the inhibition of Wnt and non-Smad-dependent TGF-\u03b2 pathways","volume":"123","author":"Z. Azadian","year":"2021","journal-title":"Journal of Cellular Biochemistry"},{"key":"27","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2212"},{"key":"28","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s43088-020-00059-7","article-title":"In silico molecular docking studies and MM\/GBSA analysis of coumarin-carbonodithioate hybrid derivatives divulge the anticancer potential against breast cancer","volume":"9","author":"S. V. Pattar","year":"2020","journal-title":"Beni-Suef University Journal of Basic and Applied Sciences"},{"key":"29","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2019.103612"},{"key":"30","volume-title":"Methicillin Resistant Staphylococcus aureus","author":"A. H. Siddiqui","year":"2021"},{"key":"31","first-page":"2759","article-title":"Recent progress regarding kaempferol for the treatment of various diseases","volume":"18","author":"J. Ren","year":"2019","journal-title":"Experimental and Therapeutic Medicine"},{"key":"32","doi-asserted-by":"crossref","first-page":"2383","DOI":"10.1007\/s00217-020-03582-0","article-title":"Kaempferol separated from Camellia oleifera meal by high-speed countercurrent chromatography for antibacterial application","volume":"246","author":"Y. Qiu","year":"2020","journal-title":"European Food Research and Technology"},{"key":"33","doi-asserted-by":"publisher","DOI":"10.1007\/s13205-021-02880-y"},{"key":"34","doi-asserted-by":"publisher","DOI":"10.1016\/j.lwt.2007.06.010"},{"key":"35","doi-asserted-by":"crossref","DOI":"10.1111\/jfbc.12579","article-title":"Analysis of rutin, \u03b2-carotene, and lutein content and evaluation of antioxidant activities of six edible leaves on free radicals and reactive oxygen species","volume":"42","author":"K. Gunathilake","year":"2018","journal-title":"Journal of Food Biochemistry"},{"key":"36","volume-title":"Nonvitamin and Nonmineral Nutritional Supplements","author":"A. S. Silva","year":"2019"},{"key":"37","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2017.07.008"},{"key":"38","doi-asserted-by":"publisher","DOI":"10.3390\/plants10030475"},{"key":"39","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.00856"},{"key":"40","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/761506"},{"key":"41","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2017.01.019"},{"key":"42","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.14695"},{"key":"43","doi-asserted-by":"crossref","DOI":"10.1128\/AEM.01804-18","article-title":"Amentoflavone ameliorates Streptococcus suis-induced infection in vitro and in vivo","volume":"84","author":"X. Shen","year":"2018","journal-title":"Applied and Environmental Microbiology"},{"key":"44","doi-asserted-by":"publisher","DOI":"10.4014\/jmb.1302.02045"},{"key":"45","volume-title":"Performance Standards for Antimicrobial Susceptibility Testing","author":"P. Wayne","year":"2011"},{"key":"46","doi-asserted-by":"publisher","DOI":"10.1249\/jsr.0b013e3181ae8959"},{"key":"47","article-title":"Beneficial effects of quercetin on obesity and diabetes","volume":"4","author":"L. Aguirre","year":"2011","journal-title":"The Open Nutraceuticals Journal"},{"key":"48","doi-asserted-by":"publisher","DOI":"10.3390\/nu8030167"},{"key":"49","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24061123"},{"key":"50","doi-asserted-by":"publisher","DOI":"10.1111\/1541-4337.12342"},{"key":"51","doi-asserted-by":"crossref","first-page":"84","DOI":"10.4103\/0973-7847.194044","article-title":"Overviews of biological importance of quercetin: a bioactive flavonoid","volume":"10","author":"A. V. A. David","year":"2016","journal-title":"Pharmacognosy Reviews"},{"key":"52","doi-asserted-by":"publisher","DOI":"10.4315\/0362-028x.jfp-17-214"}],"container-title":["International Journal of Microbiology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijmicro\/2022\/9130700.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijmicro\/2022\/9130700.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/ijmicro\/2022\/9130700.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T23:05:28Z","timestamp":1651705528000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/ijmicro\/2022\/9130700\/"}},"subtitle":[],"editor":[{"given":"Rossella","family":"Grande","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,5,4]]},"references-count":52,"alternative-id":["9130700","9130700"],"URL":"https:\/\/doi.org\/10.1155\/2022\/9130700","relation":{},"ISSN":["1687-9198","1687-918X"],"issn-type":[{"value":"1687-9198","type":"electronic"},{"value":"1687-918X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,5,4]]}}}