Chapter 8

Plasmepsin: Function, Characterization and Targeted

Antimalarial Drug Development

Peng Liu

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/66716

Abstract

The devastating malaria, caused by parasites of the genus Plasmodium, afflicts nearly half

of the world's population and imposes a heavy socio‐economic burden particularly to the

disease‐endemic Sub‐Saharan Africa. Sustained efforts in malaria control have been made

from the perspectives of medicine‐ and vaccine‐based prevention and treatment of malaria

and malaria transmission blockage for the past 15 years, resulting in a decreased mor‐

tality rate by 60% and a decreased malaria incidence rate by 37% globally. Nonetheless,

due to the emergence and rapid spread of drug‐resistant parasite strains, novel antima‐

larial drugs are urgently required to combat this deadly disease. Plasmepsins are deemed

potential targets for novel antimalarial drug design. Plasmepsins represent an aspartic

proteinase family that can be sub‐categorized into seven groups based on the amino acid

sequence identity. This chapter discusses our progress in understanding the biosynthesis,

biological functions and enzymatic characteristics of the plasmepsin family. This led to

development of various types of plasmepsin‐targeted compounds and the assessment of

their binding affinity and selectivity, anti‐parasitic activity and cytotoxicity. The gained

experience and current status in developing plasmepsin‐targeted antimalarial drugs are

addressed. Finally, a deeper and broader investigation on the functions and characteristics

of the plasmepsin family is encouraged.

Keywords: malaria, plasmepsin, drug design, Plasmodium, aspartic proteinase

1. Introduction

Malaria, a life‐threatening infectious disease, afflicts approximately 3.2 billion people, causes
214 million clinical cases and leads to nearly 440,000 deaths worldwide in 2015 despite the facts
that malaria mortality rates decreased by 60% globally and by 66% in Africa between 2000 and
2015, and that malaria incidence rates decreased by 37% globally and by 42% in Africa for the

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