{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T08:26:50Z","timestamp":1787128010857,"version":"build-2736575974"},"reference-count":110,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cordinaci\u00f3n de Investigaci\u00f3n e Inovaci\u00f3n of the Universidad Regional Amaz\u00f3nica Ikiam, Ecuador"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Pseudomonas aeruginosa (PA) is a clinically relevant opportunistic pathogen whose persistence and antimicrobial tolerance are largely driven by biofilm formation and quorum-sensing (QS)-regulated virulence. Targeting QS has therefore emerged as an antivirulence strategy that attenuates pathogenicity without exerting strong selective pressure on bacterial growth. This systematic review (2020\u20132024) analyzes recent advances in the identification of QS inhibitors against PA, emphasizing studies that integrate in silico approaches. Forty-six studies met the inclusion criteria. All employed molecular docking, and 36.9% (n = 17) incorporated molecular dynamics simulations. While valuable for initial detection, these computational predictions have inherent limitations in accurately estimating binding energy and conformational dynamics, requiring empirical validation to confirm actual biological activity. Approximately one-fifth of the studies were exclusively computational, whereas the remainder combined in silico screening with in vitro and, in some cases, in vivo assays. The most frequently investigated QS regulators were LasR, PqsR, and RhlR, alongside additional virulence-associated proteins. The evaluated compounds encompassed phytochemicals, synthetic molecules, nanomaterials and natural product-derived compounds, several of which demonstrated experimental evidence of biofilm attenuation and reduction in QS-regulated virulence factors. Overall, the findings highlight the value of integrating computational and experimental strategies to rationally prioritize antivirulence candidates. However, the intrinsic complexity and redundancy of the QS network suggest that future research should increasingly focus on multitarget approaches and on the exploration of chemically diverse and previously underexplored compound libraries to improve efficacy against PA biofilms.<\/jats:p>","DOI":"10.3390\/molecules31162887","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:58:23Z","timestamp":1787126303000},"page":"2887","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["In Silico Approaches Targeting Quorum-Sensing Inhibition in Pseudomonas aeruginosa: A Systematic Review"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1227-4274","authenticated-orcid":false,"given":"Yeimy","family":"Rojas","sequence":"first","affiliation":[{"name":"Carrera de Biotecnolog\u00eda, Facultad de Ciencias de la Vida, Universidad Regional Amaz\u00f3nica Ikiam, Tena 150150, Ecuador"},{"name":"Instituto Venezolano de Investigaciones Cient\u00edficas, Caracas 1020A, Venezuela"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7804-5095","authenticated-orcid":false,"given":"Cristian","family":"Sillagana-Verdezoto","sequence":"additional","affiliation":[{"name":"Master\u2019s Program in Innovation in Biosciences and Bioengineering, Faculty of Engineering, Universidad San Sebasti\u00e1n, Concepci\u00f3n 4081339, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4118-1015","authenticated-orcid":false,"given":"Jacobus de","family":"Waard","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Universidad Esp\u00edritu Santo, Samborond\u00f3n 092301, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6141-8174","authenticated-orcid":false,"given":"Cristina","family":"Quiroga","sequence":"additional","affiliation":[{"name":"Carrera de Biotecnolog\u00eda, Facultad de Ciencias de la Vida, Universidad Regional Amaz\u00f3nica Ikiam, Tena 150150, Ecuador"},{"name":"Biogeography and Spatial Ecology Research Group, Life Sciences Faculty, Universidad Regional Amaz\u00f3nica Ikiam, Tena 150150, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00248-013-0297-x","article-title":"Pseudomonas aeruginosa Biofilms in Disease","volume":"68","author":"Mulcahy","year":"2014","journal-title":"Microb. 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