Biology subjects

Marapana, D. F.

Publications and source records attributed to Marapana, D. F..

3 recordsLinked to original sources

bioRxiv2026

Targeting PTRAMP-CSS potently inhibits P. falciparum across blood, liver and mosquito stages

Malaria, caused by Plasmodium falciparum spans liver, blood, and mosquito stages, limiting the effectiveness of single-stage vaccines. The PTRAMP-CSS heterodimer, a core component of the essential PCRCR invasion complex, is expressed on merozoites, mature gametocytes, and salivary gland sporozoites, enabling single-antigen targeting across multiple lifecycle stages. Nanobodies against PTRAMP-CSS block merozoite invasion of erythrocytes, reduce mosquito infection in membrane-feeding assays, and inhibit sporozoite invasion of primary human hepatocytes. High-resolution crystal structures of inhibitory and non-inhibitory nanobody-antigen complexes identify conserved inhibitory epitopes and guide the design of bispecific nanobody Fc constructs with enhanced potency. In semi-immune Kenyan CHMI samples, higher baseline IgG to PTRAMP-CSS and Ripr is associated with improved parasite control. By demonstrating conserved vulnerability across all three major lifecycle stages, PTRAMP-CSS offers a realistic path to single-antigen, multistage vaccines and biologics that aim to prevent disease and block transmission.

microbiology↗

bioRxiv2026

Molecular basis for the role of Ripr in Plasmodium falciparum invasion of human erythrocytes

Plasmodium falciparum causes the majority of severe malaria, and merozoite invasion of erythrocytes is a vulnerable, antibody-accessible step of the blood-stage cycle. PfRipr is an essential component of the PCRCR invasion complex, yet the structural basis for antibody-mediated neutralisation remains unclear. Here, we map inhibitory and non-inhibitory epitopes across PfRipr and show that all potent inhibitors localise to the tail region (EGF6-8). Crystal structures reveal that inhibitory antibodies restrict the flexibility surrounding EGF7. Indeed, EGF7 buried surface area correlates strongly with inhibitory potency, identifying this domain as the principal invasion-inhibitory determinant. Pairwise antibody combinations revealed unexpected synergy, with non-inhibitory mAbs potentiating anti-Rh5 activity. Conditional deletion, sequence replacement or positional swapping of EGF6-8 abolished invasion, demonstrating that both sequence and spatial arrangement are indispensable. These data define EGF7 as a conserved, functionally essential vulnerability and provide a blueprint for rational EGF6-8 immunogen design capable of eliciting P. falciparum strain-transcending protection against blood-stage malaria.

biochemistry↗

bioRxiv2026

Formation of the moving junction is the nexus for host cytoskeletal remodelling during Plasmodium falciparum invasion of human erythrocytes

Plasmodium falciparum invasion of human erythrocytes is a complex and tightly coordinated process, involving host cell attachment, moving junction formation and engagement of the parasites actomyosin motor. The temporal precision of these events is mediated by distinct ligand-receptor interactions and the sequential release of the merozoites apical organelles. What remains unclear is how these molecular and biophysical interactions enable Plasmodium to bypass the stable erythrocyte membrane-cytoskeletal complex. Here, several P. falciparum lines expressing different fluorescently tagged apical organelle proteins, were imaged with lattice light sheet microscopy (LLSM) to determine the timing of cytoskeletal disassembly and apical organelle release. Blocking the AMA1-RON2 interaction has no effect on the PfRh5-basigin Ca2+ flux but prevents host cytoskeleton disassembly. In contrast, the inhibition of parasite actin polymerisation had no effect on cytoskeletal clearance but caused a sustained Ca2+ response. We further demonstrate that establishment of the moving junction is temporally linked to clearance of the host cytoskeleton. Collectively, our findings support the existence of an association between the RON complex and components of the host cytoskeleton, which mediates the localised disruption of the erythrocyte-membrane cytoskeletal complex during invasion.

microbiology↗