In-silico SCREENING OF FLAVONOIDS AS AgrA INHIBITORS BY MOLECULAR DOCKING, NORMAL MODE ANALYSIS, AND ADMET STUDY.

Excessive and prolonged intake of antibiotics results in the emergence of antibiotic-resistant pathogenic bacterial strains. As a consequence, managing bacterial infections with currently available antibiotics is extremely challenging. In order to tackle the bacterial resistance, bacterial communication mechanism, especially bacterial quorum sensing (QS) is targeted. In agr QS system, the various gene expression involved in the secretion of virulence factors can be attenuated by inhibiting the DNA-AgrA interactions. Here, we docked twenty flavonoids with previously homology modeled AgrA proteins together with PDB ID: 4G4K (template protein of the homology models) using the AutoDock tool. Out of twenty flavonoids, three flavonoids (dracorhodin, acacetin, and oroxylin A) exhibited promising binding free energies (<-9.00 kcal/mol). We also performed a normal mode analysis to check the stability of docked complexes. The best-docked complexes are stable as indicated by normal mode analyses. The best three flavonoids (dracorhodin, acacetin, and oroxylin A) possess desirable drug-likeness attributes. Hence, these compounds can act as novel AgrA inhibitors [ABSTRACT FROM AUTHOR]