BEYOND TRADITIONAL ANTIMALARIALS: UNLOCKING NEW TARGETS FOR NEXT-GENERATION MALARIA TREATMENT

Abstract

Malaria remains a significant global health challenge, with rising incidence rates and the alarming spread of drug-resistant Plasmodium strains threatening recent advances in control and eradication efforts. Current antimalarial therapies predominantly target the asexual blood stage of the parasite and are increasingly compromised by resistance, limited stage coverage, and pharmacological drawbacks. There is an urgent need for new therapeutic strategies that offer broader efficacy across different stages of the parasite's lifecycle, novel mechanisms of action, and resilience against resistance development. This review highlights emerging molecular targets in Plasmodium species, including proteases, kinases, transporters, dihydroorotate dehydrogenase (DHODH), apicoplast-associated pathways, and critical enzymes like PfATP6 and PfPI3K. Natural compounds such as flavonoids, alkaloids, and other bioactives have shown promising inhibitory activity against these targets. Advancing our understanding of these novel pathways and integrating natural product research could pave the way for the development of next-generation, resistance-resilient antimalarial therapies