Elemental zinc inhibits Plasmodium falciparum blood-stage forms and enhances the efficacy of standard antimalarial drugs in vitro.

The recent rise in malaria cases post-COVID-19 and antimalarial resistance in Plasmodium falciparum present new treatment challenges. Repurposing existing drugs or creating new combinations is an effective strategy. Elemental zinc (Zn2+) mitigates cancer progression and viral infections. However, no study has demonstrated the direct lethal effect of zinc on blood-stage P. falciparum. This study examined Zn2+ antiplasmodial effect on the blood-stage P. falciparum 3D7 strain using a time-inhibition growth assay (24, 48, 72, and 96 h) with the SYBR Green I method. The findings indicated that Zn2+ exhibited IC50 values of 49.5 and 26 µM at 72 and 96 h, respectively. When fixed Zn2+ concentrations (50 and 25 µM) were co-treated for 48 h with standard antimalarial drugs, such as chloroquine (CQ) and dihydroartemisinin (DHA), there was a notable decrease in CQ IC50 value (0.017 and 0.026 µM) and DHA IC50 value (0.007 and 0.011 µM) compared to treatment with these drugs alone. Stage-specific studies revealed that trophozoites and schizonts were highly susceptible to Zn2+ in combination with CQ or DHA. This study is the first to show that elemental Zn2+ alone impedes blood-stage parasites in a time- and stage-dependent manner and its combination with CQ or DHA improves antimalarial treatment effectiveness.