Virtual screening to identify lead inhibitors for bacterial NAD synthetase (NADs)

Virtual screening was employed to identify new drug-like inhibitors of NAD synthetase (NADs) as antibacterial agents. Four databases of commercially available compounds were docked against three subsites of the NADs active site using FlexX in conjunction with CScore. Over 200 commercial compounds were purchased and evaluated in enzyme inhibition and antibacterial assays. 18 compounds inhibited NADs at or below 100 μM (7.6% hit rate), and two were selected for future SAR studies.

Graphical abstractStructure-based virtual screening was used to identify new inhibitors of Bacillus anthracis nicotinamide adenine dinucleotide synthetase (NADs). 18 new small molecule inhibitors were identified with IC50 ⩽ 100 μM, and a new lead structural class was chosen for optimization.Figure optionsDownload full-size imageDownload as PowerPoint slide