{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T07:31:25Z","timestamp":1778657485733,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methicillin\u2010resistant\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    <\/jats:styled-content>\n                    (MRSA) poses significant therapeutic challenges due to its global spread and virulence. Targeting the critical virulence regulator ClpP presents a promising antivirulence strategy. This study investigated AMF's mechanism against MRSA through molecular dynamics simulations, FRET and TSA. Phenotypic analyses revealed AMF's inhibition of MRSA haemolytic activity (72% reduction) and biofilm formation (58% decrease) without affecting bacterial growth. Molecular docking identified key AMF\u2013ClpP interaction sites (ARG\u2010171, ASP\u2010170, ASP\u2010172), validated via CETSA. AMF reduced transcription of critical virulence genes (\n                    <jats:italic>hla, psm\u03b1<\/jats:italic>\n                    ) by 3.8\u2010fold and inhibited ClpP enzymatic activity by 65%. Cellular studies demonstrated AMF's protection of A549 lung cells from MRSA infection (82% viability vs. 43% control). In murine pneumonia models, AMF treatment enhanced survival rates from 20% to 75% while reducing proinflammatory cytokines (IL\u20106, TNF\u2010\u03b1) by 60%\u201370%. Histopathological analysis showed significant mitigation of lung tissue damage. These findings establish AMF as a potent ClpP inhibitor that attenuates MRSA virulence through dual mechanisms: suppression of toxin production and biofilm formation. The compound's therapeutic potential stems from its ability to disarm pathogenic mechanisms while maintaining commensal microbiota integrity. This study provides proof\u2010of\u2010concept for antivirulence strategies targeting ClpP, offering a promising alternative to traditional antibiotics against MRSA infections.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.70825","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T07:21:37Z","timestamp":1761117697000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Inhibitory Effect of Amentoflavone on the Virulence of\n                    <scp>MRSA<\/scp>\n                    by Targeting\n                    <scp>ClpP<\/scp>"],"prefix":"10.1111","volume":"29","author":[{"given":"Teri","family":"Gele","sequence":"first","affiliation":[{"name":"Changchun University of Chinese Medicine  Changchun China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangri","family":"Kong","sequence":"additional","affiliation":[{"name":"Endocrinology Department The 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