Abstract
Proteases are primary enzymes that are involved in parasites' host invasion by disrupting the physical barriers and immune system. Due to the mass anthelminthic drive against helminths by WHO, the occurrence and spread of drug resistance strains have increased. Taenia solium is one of the major helminthic infections to humans. The CNS infection of parasites' cysts leads to epilepsy, i.e., neurocysticercosis. The existing drugs are several decades old, and their efficacy is poor for the treatment of CNS infection. This demands one to look for new drugs for use in the near future. Detailed proteomic characterization of T. solium proteases is lacking, though they could be one of the primary targets for the development of new drugs. We used LC-MS/MS-based proteomics to characterize and identify proteases, bioinformatics to identify essential proteases, and cheminformatics tools to screen their inhibitors from the ZINC15 drug bank. Finally, we did in vitro cytotoxicity, inflammatory, and cysticidal assays for drug repurposing. We identified proteases present on cyst fluid (n = 50) and cyst wall (n = 23) and sorted seven essentials, ones that were used for docking studies with drugs. The docking studies led to five preapproved drugs, and finally two were sorted. We report 100% efficacy with 1,10-phenanthroline (metalloprotease inhibitor) and belinostat in in vitro cysticidal experiments. 1,10-Phenanthroline had better blood-brain permeability and was less cytotoxic when compared with albendazole sulfoxide and praziquantel. Thus, we propose 1,10-phenanthroline as an alternative drug for NCC. However, this needs further detailed investigation in a suitable animal model.