Natural products in antimalarial drug discovery: progress, emerging technologies, and future directions

Abstract

Malaria remains a major global health problem, caused mainly by Plasmodium falciparum and P. vivax, and is increasingly complicated by the spread of drug resistance and the limited impact of current vaccines. Natural products have played a central role in antimalarial therapy, most notably through the discovery of quinine and artemisinin, and they continue to provide an important source of bioactive chemical scaffolds. This review outlines recent progress in antimalarial drug discovery from natural products, with particular attention to advances in phytochemical isolation, structure-based drug design, and the growing use of computational methods, including molecular modelling, machine learning, and omics-based approaches. The contribution of traditional knowledge to the identification of new chemotypes and potential targets is also discussed. Key challenges, including poor bioavailability, toxicity, regulatory barriers, and pressures on biodiversity, are considered in the context of sustainability, ethical bioprospecting, and international frameworks such as the Nagoya Protocol. Finally, the review discusses practical directions for improving clinical translation, strengthening sustainable supply, and promoting equitable benefit-sharing in the continued search for new antimalarial therapies.