Targeting elongation factor 2 in Anopheles gambiae: molecular insights and implications for malaria vector control

Malaria remains one of the most devastating infectious diseases globally, with Anopheles gambiae serving as the principal vector across sub-Saharan Africa. The effectiveness of traditional vector control methods is currently under threat due to the rapid rise of pesticide resistance, which calls for the discovery of new molecular targets. The GTP-dependent GTPase known as Eukaryotic Elongation Factor 2 (EF-2; encoded by AGAP009441 in An. gambiae) is essential for cellular viability because it catalyzes the translocation stage of ribosomal protein production. EF-2 was identified as an important gene in An. gambiae by machine learning-based computational screening, and RNA interference (RNAi)-mediated knockdown experimentally verified that EF-2 silencing dramatically shortens mosquito longevity (p < 0.0001). Despite the fact that EF-2 and its human homolog share about 79% of the same protein sequence, species-specific structural characteristics may provide opportunities for selective targeting. Additionally, a comparative dN/dS analysis was carried out on EF-2 across Anopheles species using the HyPhy Datamonkey platform. The dN/dS results revealed high evolutionary conservation (ω = 0.0198) and are consistent with purifying selection, but not with positive selection. The current understanding of EF-2 biology, its validation as a vector control target, suitable intervention modalities like RNA interference and small-molecule inhibition, and the major issues of selectivity, delivery, and ecological safety that need to be resolved prior to translational application are all summarized in this review. EF-2 is a promising but understudied contender whose complete potential in integrated malaria vector control necessitates immediate and ongoing research.