In silico interaction of catalytic domain of Clostridioides difficile toxins TcdA and TcdB with some selected compounds from the SuperNatural 3.0 database

Clostridioides difficile is a pathogenic bacterium responsible for antibiotic-associated diarrhea globally. The pathogenesis of this bacterium is due to its virulence toxins, which inactivate the small GTPases from the Rho and Ras families in host cells, leading to the establishment of Clostridioides difficile infection. In a bid to avert this infection, compounds from SuperNatural 3.0 were screened against the catalytic glucosyltransferase domains of TcdA and TcdB using molecular docking analysis. The enzymes and the compounds were imported into the PyRx virtual screening software and docked accordingly. Post-docking interactions were visualized using Discovery Studio software. The binding energies resulting from the interaction of the compounds and the enzymes were within the range of −8.9 to −11.4 kcal/mol and −7.6 to −11.2 kcal/mol for TcdA and TcdB respectively, suggesting fairly strong binding affinities. Ligands that have the potential to be considered for drug discovery have binding energy less than −6.0 kcal/mol (or −8.0 kcal/mol in some cases). This is associated with the hydrogen bonds and other interactions between the molecules and the amino acids found within the toxins. The pharmacokinetic profiling revealed the compounds to be relatively safe, with SN0161212, SN0032215, and SN0084749 passing Lipinski's rule of five, with none predicted to cause human hepatotoxicity or drug-induced liver injury. The findings from this research suggest that the SuperNatural 3.0 compounds (SN0161212, SN0032215, and SN0084749) possessed the potential to inhibit Clostridioides difficile toxins. Hence, the compounds could serve as a stepping stone in designing potent inhibitor(s) against Clostridioides difficile toxins. • Natural compounds were identified using molecular docking. • Their interaction with Clostridioides difficile toxins was determined. • Compounds from SuperNatural 3.0 were screened against TcdA and TcdB toxins. • SuperNatural 3.0 compounds (SN0161212, SN0032215, and SN0084749) were detected. • The compounds were inhibitory against Clostridioides difficile toxins.