Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5)-basigin (BSG) complex (PfRH5-BSG)

The interaction between Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) and the human erythrocyte receptor basigin (CD147) is an essential and universal step for the invasion of human red blood cells by the malaria parasite (Crosnier et al., 2011, Nature). Unlike other invasion pathways that are redundant, the PfRH5-basigin axis is indispensable across all known strains of P. falciparum, making it a high-priority target for blood-stage malaria vaccines and therapeutic antibodies (Wright et al., 2014, BMC Biology). PfRH5 is a secreted parasite protein that forms a complex with other proteins, such as CyRPA and RIPR, before binding to the distal Ig-like domain of basigin on the host cell surface (Galaway et al., 2017, Nature Communications). Disrupting this protein-protein interaction prevents the parasite from entering the erythrocyte, thereby halting the asexual replication cycle responsible for clinical malaria symptoms (Douglas et al., 2011, Nature Communications). Current drug development efforts focus on inducing or administering neutralizing antibodies, such as the RH5.1 vaccine candidate, that sterically hinder the formation of the PfRH5-basigin complex (Draper et al., 2018, Cell Host & Microbe). While targeting the parasite protein PfRH5 is considered safe due to its high conservation and lack of human homologs, direct inhibition of the human basigin receptor poses significant safety challenges due to its broad expression in various tissues and its role in physiological processes like blood-brain barrier integrity (Zen et al., 2005, Journal of Biological Chemistry).

Other names

PfRH5-CD147 interactionRH5-Basigin complexReticulocyte-binding protein homolog 5-Basigin interactionPfRH5-BSG axis

Inhibition of parasite invasion via neutralization of PfRH5 or blocking of the Basigin binding site.