Structure-based Approaches Targeting Parasite Cysteine Proteases

Rafael     Pinto    Vieira; Viviane    Corrêa     Santos; Rafaela    Salgado     Ferreira
doi:10.2174/0929867324666170810165302
Abstract

Cysteine proteases are essential hydrolytic enzymes present in the majority of organisms, including viruses and unicellular parasites. Despite the high sequence identity displayed among these proteins, specific structural features across different species grant distinct functions to these biomolecules, frequently related to pathological conditions. Consequently, their relevance as promising targets for potential specific inhibitors has been highlighted and occasionally validated in recent decades. In this review, we discuss the recent outcomes of structure-based campaigns aiming the discovery of new inhibitor prototypes against cruzain and falcipain, as alternative therapeutic tools for Chagas disease and malaria treatments, respectively. Computational and synthetic approaches have been combined on hit optimization strategies and are also discussed herein. These rationales are extended to additional tropical infectious and neglected pathologies, such as schistosomiasis, leishmaniasis and babesiosis, and also to Alzheimer’s Disease, a widespread neurodegenerative disease poorly managed by currently available drugs and recently linked to particular physiopathological roles of human cysteine proteases.
Keywords: Structure-based strategies, cysteine proteases, cruzain, falcipain, human cathepsins, tropical infectious diseases, Alzheimer's Disease.
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DOI https://dx.doi.org/10.2174/0929867324666170810165302	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
Current Medicinal Chemistry

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