Computer-Aided Discovery of Compounds With Anti-Schistosomal Potential.

Schistosomiasis, which causes over 200 000 deaths annually, has since the 1970s been controlled by praziquintel. The reliance on a single drug to combat schistosomiasis, and reports of laboratory resistance to the drug, has created an urgent need in the scientific community to develop new chemotherapies to complement or supplement praziquantel. Medicinal plants are a potential reservoir of compounds with schistosomicidal activity. In the current study, we carried out computer-aided screening of compounds to discover compounds with potential to inhibit purine nucleoside phosphorylase (PNP). Thus, 99 compounds retrieved from Lotus Natural Compounds Database were docked into the active site of PNP. The top-ranked compounds were subjected to Lipinski's druglikeness and toxicity risk predictions. Three lead compounds, abrusogenin, cirsimaritin and hispidulin, were identified as having high binding affinities, favourable interactions with PNP active site residues and good toxicity risk prediction results. Molecular dynamics (MD) simulations were used to assess the stability of the interactions of these lead compounds with PNP. Collectively, analyses of the MD trajectories confirms that the lead compounds bound and interacted stably with active site residues of PNP. We conclude that abrusogenin, cirsimaritin and hispidulin could serve as hit compounds for the development of new antischistosomal drugs, based on plant-derived natural products. However, experimental studies are required to further evaluate the potentials of these compounds as possible therapeutics against schistosomiasis.