Protease inhibitors in potential drug development for Leishmaniasis.

Leishmaniasis is a deadly protozoan parasitic disease affecting millions of people worldwide. The treatment strategy of Leishmania infection depends exclusively on chemotherapy till date. But the treatment of the disease is greatly hampered due to high cost, toxicity of the available drugs and more importantly emergence of drug resistance. Hence the potential new drugs are highly needed to combat this disease. The first and foremost step of the drug discovery process is to search and select the putative target in a specific biological pathway in the parasite that should be either unambiguously absent in the host or considerably different from the host homolog. Importantly, Leishmania genome sequences enrich our knowledge about Leishmania and simultaneously reinforce us to identify the ideal drug targets that distinctly exist in the parasite as well as to develop the effective drugs for leishmaniasis. Though the leishmanial research has significantly progressed during the past two decades, the identification of suitable drug targets or development of effective drugs to combat leishmaniasis is far from satisfactory. Enzymatic systems of Leishmania metabolic and biochemical pathways are essential for their survival and infection. Concurrently, it is noteworthy that Leishmania proteases, especially the cysteine proteases, metalloproteases and serine proteases have been extensively investigated and found to be indispensable for the survival of the parasites and disease pathogenesis. Herein, we have discussed the importance of few enzymes, particularly the Leishmania proteases and their inhibitors as promising candidates for potential development of anti-leishmanial drugs.