Structure-Based Virtual Screening: Identification of Novel Quorum-Sensing Inhibitors To Interfere With the Formation of Pseudomonas Aeruginosa Biofilm

Background: drug-resistant pseudomonas aeruginosa (p. aeruginosa) isamongthe most important opportunistichumanpathogens that may infect military personnel during war by generating a broad range of virulence factors, the expression rates of which are firmly arranged by cell density-dependent cell-to-cell signaling called quorum sensing (qs). objectives: this study aimed at identifying putative inhibitors of lasr by structure-based virtual screening on zinc database, testing prospective candidatesonpqse withcomputer aided inhibition studies followed by structure analysis, andexamining the extension of specific drugs with potential anti-virulence properties for the treatment of infections induced by drug-resistant p. aeruginosa. methods: structure-based virtual screening in zinc database was used through autodock vina in order to assess putative inhibitors of lasr. prospective candidates’ inhibitoryefficiencyonpqsewasexaminedbymeansof computeraided inhibition studies followed by structure analysis. results: twenty possible quorum sensing inhibitors were introduced that could be used in different conditions to inhibit quorum sensing and thus reduce bacterial resistance and pathogenicity. a software was also designed to provide graphical user interface to vina and to automate the process of virtual screening. conclusions: this study provided a perspective for development of specific drugs with potential anti virulence properties in military medicine for the treatment of infections induced by drug-resistant p. aeruginosa