Drug Targets for Plasmodium Falciparum: Historic to Future Perspectives

This book offers a comprehensive exploration of malaria, a life-threatening disease affecting millions globally, with a focus on the parasitic organisms of the genus Plasmodium that cause it. It discusses the challenges posed by the disease, especially in economically developing regions, and delves into the biology and pathophysiology of the Plasmodium species, including their genetic flexibility and resistance to treatments. Special attention is given to P. falciparum, the most dangerous of these parasites, detailing its complex life cycle, interaction with human hosts, and the severe clinical manifestations it can induce. The book further explores the global health concern of antimalarial drug resistance, highlighting the WHO’s efforts in combating the disease and the necessity for novel treatments. Innovative research directions, such as targeting the unique organelles of Plasmodium like the apicoplast and employing proteasome inhibitors, are thoroughly examined as potential strategies in the development of new antimalarial drugs. Additionally, it addresses the critical role of the hemoglobin digestion process in the parasite’s lifecycle, presenting it as a promising target for therapeutic intervention. This work is an essential resource for researchers, clinicians, and policymakers involved in malaria control and drug development, providing insights into the current challenges and future directions in the fight against this endemic disease.

Dr Pawan Malhotra’s group at ICGEB has been involved in understanding malaria parasite biology with an aim to identify new drug and vaccine targets. Recently the group has demonstrated Plasmodium Heme Detoxification Protein (HDP) protein as a target for new drug discovery (J. Med Chem. 2017). Earlier, the laboratory illustrated a hemoglobin degradation and Hemozoin (Hz) formation complex and showed the mode of action of two current anti-malarials; chloroquine and artimisinin. Presently they are working on the discovery new class of antimalarials that act on this pathway. A part of this work has been published in Proc Natl Acad Sci, USA, 2013. Dr Malhotra’s group has illustrated ＂Methylene＂ of Plasmodium falciparum for the first time at asexual blood stages. The group has performed systematic studies to identify 27 novel secretory proteins with adhesive, immunomodulatory and signaling domains and characterized two of these proteins; PfDegP and PfCCp1 for their roles in combating oxidative/thermal stresses. (Mol. Cell. Prot, 2009; FEBS J, 2013 & Biochem J, 2018). The group has also been involved in identifying novel receptor-ligand interactions with an aim to develop an efficacious malaria vaccine or drug that can block merozoite invasion of human RBCs. They identified ICAMs and Cyclophilin B as common receptors for the invasion of Mtb and malaria into their respective hosts (Nat Comm. 2015; 2017). In addition, they recently have shown a novel gliding complex in P. falciparum that can be targeted for new antimalarial discovery.

Dr. Mohammed Tarique is a Dr. D.S. Kothari Postdoctoral Fellow at the Center for Interdisciplinary Research in Basic Sciences (CIRBSc), Jamia Millia Islamia, India. Holding a Ph.D. in Plasmodium Biology from the International Centre for Genetic Engineering and Biotechnology, New Delhi, India, his research focuses on understanding the biology of plasmodium towards the development of novel drugs. He has published more than 20 research articles in leading peer-reviewed international journals. Currently serves on the editorial boards of numerous journals, including the International Research Journal of Engineering and Technology, American Journal of BioScience, and Cell & Cellular Life Sciences Journal.