Computational identification of plant microRNAs targeting <i>Plasmodium falciparum</i>: a new strategy to address the challenges of modern malaria treatment

Malaria remains one of the greatest challenges to global health, with Plasmodium falciparum responsible for the majority of severe cases and deaths, despite significant progress in diagnosis and treatment. Resistance to antimalarial drugs, particularly associated with P. falciparum kelch13 (PfK13) mutations in Africa, as well as resistance to partner drugs such as piperaquine and lumefantrine, and limited efficacy of vaccines, necessitate the search for new therapeutic approaches. This review analyzes the current challenges in malaria treatment, focusing on the role of microRNAs (miRNAs) as potential regulators of the immune response and potential therapeutic targets. Special attention is paid to the computational screening of plant miRNAs that have promise in suppressing the expression of parasitic genes in P. falciparum. We reviewed recent literature on the molecular mechanisms of antimalarial drug resistance and the potential applications of miRNAs in malaria therapy, focusing on host- and parasite-derived miRNAs, their roles in pathogenesis, and experimental therapeutic strategies, including nanoparticle-mediated miRNA delivery. Emerging data indicate that specific host miRNAs (e.g., miR-451, miR-223) can modulate erythrocytic invasion, inflammatory responses, and disease outcomes. In parallel, advances in RNA-based therapeutics demonstrate the feasibility of miRNA mimics and inhibitors as adjunctive tools to complement existing antimalarial regimens. The integration of miRNA-based approaches into malaria therapy represents a promising frontier that could overcome the limitations of conventional drug-based strategies. Future research should prioritize the functional characterization of miRNAs, optimization of delivery systems, and evaluation of combinatorial therapies to enhance clinical translation.