Pathogenic microorganisms are persistently expressing resistance towards present generation
antibiotics and are on the verge of joining the superbug family. Recent studies revealed that, notorious pathogens such as Salmonella typhi, Shigella dysenteriae and Vibrio cholerae have acquired multiple drug resistance and the treatment became a serious concern. This necessitates an alternative therapeutic
solution. Present study investigates the utility of computer aided method to study the mechanism of receptor-
ligand interactions and thereby inhibition of
virulence factors (
shiga toxin of Shigella dysenteriae,
cholera toxin of Vibrio cholerae and
hemolysin-E of Salmonella typhi) by novel phytoligands. The rational designs of improved
therapeutics require the crystal structure for the
drug targets. The structures of the virulent toxins were identified as probable
drug targets. However, out of the three virulent factors, the structure for
hemolysin-E is not yet available in its native form. Thus, we tried to model the structure by homology modeling using Modeller 9v9. After extensive literature survey, we selected 50 phytoligands based on their medicinal significance and
drug likenesses. The receptor-
ligands interactions between selected leads and toxins were studied by molecular docking using Auto Dock 4.0. We have identified two novel
sesquiterpenes,
Cadinane [(1S, 4S, 4aS, 6S, 8aS)- 4- Isopropyl- 1, 6- dimethyldecahydronaphthalene] and
Cedrol [(8α)-Cedran-8-ol] against Shiga (binding energy -5.56 kcal/mol) and
cholera toxins (binding energy -5.33 kcal/mol) respectively which have good inhibitory properties. Similarly, a natural Xanthophyll,
Violaxanthin [3S, 3'S, 5R, 5'R, 6S, 6'S)-5, 5', 6, 6'-Tetrahydro-5, 6:5', 6'-diepoxy-β, β-
carotene-3, 3'-diol] was identified as novel therapeutic lead for
hemolysin-E (binding energy of -5.99 kcal/mol). This data provide an insight for populating the pool of novel inhibitors against various
drug targets of superbugs when all current generation drugs seem to have failed.