Targeting the Plasmodium Lifecycle: Advances and Challenges in Antimalarial Drug Development

Twesigye Davis

Department of Pharmacognosy Kampala International University Uganda

Email: twesigyedavis@studwc.kiu.ac.ug

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

CITE AS: Twesigye Davis (2025). Targeting the Plasmodium Lifecycle: Advances and Challenges in Antimalarial Drug Development IDOSR JOURNAL OF APPLIED SCIENCES 10(2):95-100, 2025. https://doi.org/10.59298/IDOSRJAS/2025/102.95100