Therapeutic target mapping from the genome of Kingella negevensis and biophysical inhibition assessment through PNP synthase binding with traditional medicinal compounds

Kingella negevensis belongs to the Neisseriaceae family. It is implied that it has significant virulence potential due to RTX toxin production, which can cause hemolysis. It usually colonizes the orophayrynx of pediatric population, along with Kingella kingae but has also been isolated from vagina. Todate no report on its drug targets is present, therefore putative therapeutic targets were identified from its genomic sequence data. Traditional Chinese (n > 36,000) and Indian medicinal compounds (n > 2000) were then screened against its pyridoxine 5'-phosphate synthase, a vital therapeutic target. Prioritized TCM compounds included ZINC02525131, ZINC33833737 and ZINC85486932, and Cadiyenol, 9,11,13-Octadecatrienoic acid and 6-Gingerol from Indian medicinal library. Molecular dynamics simulation of top compounds revealed ZINC02525131 as having best stability for 100 ns, compared to Cadiyenol. ADMET profiling was then done, along with physiologically based pharmacokinetic simulation of these compounds in a population of 200 individuals, for 12 h to see fate of the ingested compound. Additionally, the impact of these compounds in a population with cirrhosis and renal impairment was also simulated. We imply in light of all the studied parameters of safety and bioavailability, etc., that 6-Gingerol from Zingiber officinalis rhizome must be proceeded further for in vitro and in vivo testing for inhibition of K. negevensis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11030-023-10604-y.