Discovery of novel natural products as rhodesain inhibitors for human African trypanosomiasis using in silico techniques.

Human African Trypanosomiasis (HAT) or sleeping sickness is caused by the Trypanosoma brucei rhodesiense, a subspecies of the Trypanosomatide family. The parasite is associated with high morbidity and mortality rate in both animals and humans, claimed to be more fatal than other vector-transmitted diseases such as malaria. The majority of existing medications are highly toxic, not effective in the late chronic phase of the disease, and require maximum dosages to fully eradicate the parasite. In this study, we used computational methods to find out natural products that inhibit the Rhodesain, a parasitic enzyme that plays an important role in the parasite's pathogenicity, multiplication, and ability to pass through the host's blood-brain barrier. A library of 270540 natural products from ZINC databases was processed by using e-pharmacophore hypnosis and screening procedures, molecular docking, ADMET processes, and MM-GBSA calculations. This led to the identification of 3 compounds (ZINC000096269390, ZINC000035485292, and ZINC000035485242) which were then subjected to molecular dynamics. The findings of this study showed excellent binding affinity and stability toward the Rhodesain and suggest they may be a hopeful treatment for HAT in the future if further clinical trials were performed.Communicated by Ramaswamy H. Sarma.