In silico study revealed the inhibitory activity of selected phytomolecules of C. rotundus against VacA implicated in gastric ulcer

Gastric ulcer is associated with weakening of the mucous coating of the stomach and damages to the intestinal lining. It is caused by H. pylori assisted by enzymes including VacA, which necessitates the need for inhibitors of VacA. Bioactive compounds from Cyperus rotundus have been documented to have anti-inflammatory activities. However, the mechanism of action of the phytochemicals is not characterized. This research aimed to assess, in silico, the potential of selected bioactive compounds against VacA based on the binding to its active sites. VacA and bioactive compounds structures were obtained from protein database and PubChem webserver, respectively. All compounds, including 2 controls, omeprazole and cimetidine were docked against the protein using AutoDock Vina and screened based on the binding energy. The selected complexes were subjected to pharmacokinetics and toxicity screening. Finally, molecular dynamics simulation and MMPBSA were carried out on two best compounds. 17 compounds interacted with the active site of VacA with higher binding affinities, with 7 of them - aureusidine, catechin, chlorogenic acid, isorhamnetin, isovitexin, oreintin, and vitexin having the best behaviours based on ADMET and druglikeness screening. Molecular dynamics and MMPBSA experiments of two of the hits corroborated good stability and binding energy for Ellagic Acid and Scirpusin B (Delta G = -14.38 and -13.20 kcal mol(-1), respectively). These phytochemicals showed good pharmacokinetic profiles with respect to the control drugs. This study revealed that the identified compounds of C. rotundus may serve as VacA inhibitors and may be potent candidates for novel drug formulations in gastric ulcer treatment.Communicated by Ramaswamy H. Sarma