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Cysteine proteases: Battling pathogenic parasitic protozoans with omnipresent enzymes
Aadish Rawat1, Mrinalini Roy1, Anupam Jyoti1
1Amity Institute of Biotechnology, Amity University Rajasthan, Kant Kalwar, NH-11C, Jaipur-Delhi Highway, Jaipur, India.
Abstract:
Millions of people worldwide lie at the risk of parasitic protozoic infections that kill over a million people each year. The rising inefficacy of conventional therapeutics to combat these diseases, mainly due to the development of drug resistance to a handful of available licensed options contributes substantially to the rising burden of these ailments. Cysteine proteases are omnipresent enzymes that are critically implicated in the pathogenesis of protozoic infections. Despite their significance and druggability, cysteine proteases as therapeutic targets have not yet been translated into the clinic. The review presents the significance of cysteine proteases of members of the genera Plasmodium, Entamoeba, and Leishmania, known to cause Malaria, Amoebiasis, and Leishmaniasis, respectively, the protozoic diseases with the highest morbidity and mortality. Further, projecting them as targets for molecular tools like the CRISPR-Cas technology for favorable manipulation, exploration of obscure genomes, and achieving a better insight into protozoic functioning. Overcoming the hurdles that prevent us from gaining a better insight into the functioning of these enzymes in protozoic systems is a necessity. Managing the burden of parasitic protozoic infections pivotally depends upon the betterment of molecular tools and therapeutic concepts that will pave the path to an array of diagnostic and therapeutic applications.
Insights
Drug resistance in parasitic protozoan infections necessitates new treatments. Cysteine proteases are key targets, and tools like CRISPR-Cas offer new research avenues for malaria, amoebiasis, and leishmaniasis.
Area of Science:
- Parasitology
- Molecular Biology
- Drug Discovery
Background:
- Parasitic protozoan infections cause significant global mortality, with rising drug resistance limiting treatment options.
- Cysteine proteases are crucial for protozoan pathogen survival and are druggable targets, yet remain underexplored clinically.
- Malaria, amoebiasis, and leishmaniasis, caused by Plasmodium, Entamoeba, and Leishmania, respectively, represent major protozoan disease burdens.
Purpose of the Study:
- To review the role of cysteine proteases in Plasmodium, Entamoeba, and Leishmania pathogenesis.
- To highlight cysteine proteases as promising therapeutic targets for protozoan diseases.
- To explore the potential of molecular tools like CRISPR-Cas for studying these enzymes and protozoan function.
Main Methods:
- Literature review focusing on cysteine proteases in Plasmodium, Entamoeba, and Leishmania.
- Analysis of current therapeutic challenges and drug resistance mechanisms.
- Discussion of CRISPR-Cas technology for genomic exploration and functional studies.
Main Results:
- Cysteine proteases are essential for the lifecycle and virulence of key protozoan parasites.
- Existing therapies face challenges due to widespread drug resistance.
- CRISPR-Cas technology offers a powerful approach to investigate protozoan biology and validate cysteine proteases as drug targets.
Conclusions:
- Targeting cysteine proteases is a viable strategy to combat parasitic protozoan infections.
- Advancements in molecular tools are crucial for understanding protozoan enzymes and developing novel diagnostics and therapeutics.
- Overcoming research hurdles is essential for managing the global burden of these diseases.
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