We investigated 1012 molecules from natural products previously isolated from the South African biodiversity (SANCDB, https://sancdb.rubi.ru.ac.za/), for putative inhibition of Onchocerca volvulus pi-class glutathione S-transferase (Ov-GST2) by virtual screening, MMGBSA, and molecular dynamics approaches. ADMET, docking, and MMGBSA shortlisted 12 selected homoisoflavanones-type hit molecules, among which two namely SANC00569, and SANC00689 displayed high binding affinities of −46.09 and −46.26 kcal mol−1, respectively towards π-class Ov-GST2, respectively. The molecular dynamics results of SANC00569 showed the presence of intermolecular H-bonding, hydrophobic interactions between the ligand and key amino acids of Ov-GST2, throughout the simulation period. This hit molecule had a stable binding pose and occupied the binding pockets throughout the 200 ns simulation. To the best of our knowledge, there is no report of any alleged anti–onchocerciasis activity referring to homoisoflavanones or flavonoids. Nevertheless, homoisoflavanones, which are a subclass of flavonoids, exhibit a plethora of biological activities. All these results led to the conclusion that SANC00569 is the most hypothetical Ov-GST2, which could lead the development of new drugs against Onchocerca volvulus pi-class glutathione S-transferase. Further validation of these findings through in vitro and in vivo studies is required.

In this study, we screened novel dipeptidyl peptidase IV (DPP4) inhibitors from the ConMedNP library consisting of 3507 molecules. Interestingly, molecular docking, ADMET, and the anti-diabetic activity predictions suggest that three molecules, namely OTH_UD_XX06_1, GB19, and BMC_000104, have a high binding affinity toward DPP4. The molecular dynamics (MD) simulation results suggest that these hit molecules have a stable binding pose and occupy the binding pockets throughout the 200 ns simulation. The presence of intermolecular H-bonding between the ligands and DPP4 was observed throughout the simulation period. Thus, docking and MD results, predicted that the three compounds were the most potent DPP4 inhibitors that could putatively bind to the DPP4 active site via both conventional H-bonding and hydrophobic interactions. These results could aid the discovery of new drugs to treat type 2 diabetes.