Therapeutic Targeting and Role of Cysteine Proteases in the Life Cycle of Malaria Parasite

Author:

Uddin Amad12,Ara Anam1,Thaer Abdulhameed Haider12,Gupta Sonal2,Arora Smriti3,Singh Shailja2,Abid Mohammad1

Affiliation:

1. Medicinal Chemistry Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India

2. Host-Parasite Interaction Biology Laboratory, Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India

3. University of Petroleum & Energy Studies (UPES), Energy Acres Building, Bidholi, Dehradun-248007, Uttarakhand, India

Abstract

The malaria parasite Plasmodium expresses four related papain-family cysteine proteases. Targeting these different cysteine proteases can elucidate their roles and potential as therapeutic targets, thereby expanding the pool of antimalarial targets. During gametogenesis, cysteine proteases like SERA-5, SERA-3, DPAP-1, DPAP-2, DPAP- 3, and Falcipain-1 are required for parasitophorous vacuole membrane (PVM) rupture. In the liver stage, cysteine proteases such as Falcipain-1 and SERA-3, SERA-4, SERA-5, and SERA-6 are essential. Additionally, cysteine proteases like DPAP-3, Falcipain- 1, Falcipain-2, Falcipain-3, and SERA-5, SERA-6 play crucial roles in merozoite invasion into red blood cells (RBCs), hemoglobin degradation, and merozoite release from RBCs. This review summarizes the available literature describing the key roles of various cysteine proteases in the life cycle of the malaria parasite and their potential as targets for antimalarial therapy. Understanding these proteases could aid in developing novel antimalarial treatments and overcoming drug resistance.

Publisher

Bentham Science Publishers Ltd.

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