Background: Schistosomiasis is a parasitic protozoal disease caused by flatworms of the
genus Schistosoma. Although the disease threatens millions of lives, it is still at the top list of neglected
tropical diseases and praziquantel, the only common schistosocidal drug in use, has records of
decreasing efficiency and cases of resistance. Also, reports revealed that people in the rural areas, who
are most affected, rely mostly on traditional herbal medicines because of limited access to modern
healthcare. The use of computers in drug development has become a routine practice because they are
cost and time effective.
Objective: We used computational techniques to discover potent Schistosoma inhibitors of natural
Methods: Computer-based techniques were employed to discover anti-schistosoma lead/hit from plant
metabolites isolated from African medicinal plants which have shown activity or are responsible for
activity against Schistosomes. The plant metabolites were evaluated for ‘drug-likeness’ and docked
toward four selected validated Schistosoma drug targets; Glutathione S-transferase, Thioredoxin glutathione
reductase, Histone deacetylase and Schistosoma masoni arginase, with PDB codes: 1M9A,
2X99, 4BZ8 and 4Q3T respectively.
Results: A total of 27 bioactive compounds with anti-Schistosoma history were retrieved from literature.
The phytochemicals with Lipinski violation of ≤ 2 were found to exhibit comparable binding affinities
toward the studied targets as the co-crystallized inhibitors. Predicted binding modes of the
compounds toward respective target showed key intermolecular interactions involved in the ligandtarget
relationship. Moreover, one of the compounds emerged as the most interesting candidate by
both being drug-like and inhibiting the activities of the studied enzyme targets at micro-molar range.
Conclusion: Our study identified schistosocidal leads with high bioavailability profile and the exploration
of binding modes could lay the foundation for synthetic modification of the plant metabolites
for the development of novel anti-schistosoma drug(s) with new mechanism of action.