Abstract

Malaria remains one of the world’s most devastating infectious diseases, caused by Plasmodium parasites transmitted 
through Anopheles mosquitoes. Despite global efforts to reduce its burden, resistance to existing antimalarial drugs 
threatens to reverse progress, prompting the need for novel therapeutic strategies. Targeting the complex 
Plasmodium lifecycle-spanning the liver, blood, and mosquito stages-offers multiple intervention points. This review 
explores recent advances in antimalarial drug development with a focus on lifecycle-specific targets. Key 
breakthroughs include new endoperoxides, mitochondrial inhibitors, and transmission-blocking agents. 
Additionally, emerging platforms such as proteomic screening, CRISPR-Cas9 gene editing, and structure-based 
drug design have accelerated the identification of promising compounds. However, challenges such as drug 
resistance, toxicity, limited efficacy across all lifecycle stages, and translational hurdles from bench to bedside persist. 
A multipronged approach, combining stage-specific therapies, host-targeted interventions, and strategic drug 
combinations, is critical for sustainable malaria control and eventual eradication. 
Keywords: Plasmodium lifecycle, antimalarial drug development, drug resistance, transmission-blocking agents, 
liver-stage therapeutics