Natural products as Potential Inhibitors of APH(3')-IIIa of <em>Enterococcus faecalis</em>: An <em>In-silico</em> Perspective

• DOI: 10.20944/preprints202211.0132.v1
• Publication Date: 2022-11-08T09:14:05Z
• Authors: Juan Marcelo Carp...; Juliana Carolina ...
• Keywords: Enterococcus faecalis; Docking (animal)

Enterococcus faecalis is a bacterium that can develop multidrug resistance profile associated with the community as well nosocomial-acquired infections. Among treatment options for these infections are aminoglycosides combined bacterial cell wall inhibitors such beta-lactams, since E. intrinsically resistant to aminoglycosides. One of its most representative mechanisms expression aminoglycoside-modifying enzymes, aminoglycoside phosphotransferase type IIIa (EfAPH(3')-IIIa). This enzyme acts by phosphorylating in an ATP-dependent reaction, modifying 3' position hydroxyl groups antibiotics. Considering this scenario, 3,092 natural products obtained from ZINC22 database were analyzed select molecules highest affinity nucleotide-binding pocket EfAPH(3')-IIIa, which could be potential adjuvants. The showed best-score results ensemble docking-based virtual screening ZINC000000952700 (BS-1), ZINC000014793040 (BS-2) and ZINC000015498603 (BS-3). promising BS-2, flavone derivative, due improved stability molecular dynamics simulation (average values RMSD 0.23 nm, Rg 1.94 nm), binding free energy calculations &amp;Delta;G total -35.3 better toxicological (lower probability hepatotoxicity, carcinogenic, immunotoxicity, mutagenicity, cytotoxicity effects), compared BS-1 BS-3. These allow us propose derivative may act adjuvant infections, acting inhibitor EfAPH(3')-IIIa.