Background: Human Onchocerciasis, caused by the filarial nematode Onchocerca volvulus infection, is a neglected public health disease that affects millions of people in the endemic regions of sub-Saharan Africa and Latin America. It is also called river blindness because the Black flies that transmit infection breeds in rapidly flowing fresh water streams and rivers. The disease is second to trachoma as the leading cause of blindness due to infection in the developing world and only few drugs are commonly used to treat nematode infections, creating a dangerous environment for the emergence of drug resistance. The study aims to identify essential drug targets in Onchocerca volvulus and its endosymbiont (Wolbachia pipientis) and repurpose existing drugs with inhibitory activities against the drug targets.Methods: Through molecular docking simulations, 2,015 approved drugs were screened against two critical protein targets: Glutamate Chloride ion gated channel and 30s ribosomal protein using Autodock-vina. Protein targets of frontrunner drugs were also evaluated using the Swiss target prediction server. The drugs’ interactions with the target proteins were analyzed using Discovery Studio Visualizer. Molecular dynamics was executed using Schrödinger LLC Desmond software.Results: The study identified Adapalene, Diosmin and Azelastine as promising multi-target drugs based on their binding affinities and potential to inhibit the Onchocerca volvulus and Wolbachia pipientis targets. Additionally, other compounds like Drospirenone, Alectinib, Dutsteride and finasteride showed significant potential and warrant further investigation.Conclusion: The findings suggest that repurposing these drugs could provide an accessible and effective therapeutic option for onchocerciasis and broaden the range of treatment options. Further studies are recommended to validate the efficacy of these drugs against Onchocerciasis.
Gabriel et al. (Sat,) studied this question.