Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Successful Plasmodium falciparum invasion of red blood cells includes the orderly execution of highly specific receptor-ligand molecular interactions between the parasite's proteins and the red blood cell membrane proteins. There is a growing need for elucidating receptor-ligand pairings, which will help in understanding the parasite's biology and provide the fundamental basis for developing prophylactic or therapeutic alternatives leading to mitigating or eliminating this type of malaria. We have thus used Plasmodium falciparum RH5 - derived peptides and ghost red blood cell proteins in synthetic peptide affinity capture assays to identify important host receptors used by Plasmodium spp. in the invasion of red blood cells. LC-MS/MS analysis confirmed the extensively described interaction between PfRH5 and the basigin receptor on the red blood cell membrane. As shown here, tagged synthetic peptides displaying high binding ability to erythrocytes can be used to identify receptors present in protein extracts from ghost red blood cells via affinity capture and LC-MS/MS. SIGNIFICANCE: The article describes a novel approach for identifying red blood cell receptors based on the ability of synthetic peptides having high red blood cell binding capacity to capture Plasmodium spp. receptors on proteins extracted from ghost red blood cells. Specifically, novel methods to identify Plasmodium falciparum reticulocyte binding protein homolog 5 PfRH5 and basigin interaction using a combination of affinity capture and LC-MS/MS assays is described. Identification of these host RBC receptors interacting with malarial parasite proteins is of utmost importance in studying the disease's pathogenesis and will provide crucial information in understanding the parasite's biology. In addition, data from these studies can be used to identify potential therapeutic target(s) to mitigate or eliminate this debilitating disease.
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PMID:A novel platform for peptide-mediated affinity capture and LC-MS/MS identification of host receptors involved in Plasmodium invasion. 3304 31

The P. falciparum parasite, responsible for the disease in humans known as malaria, must invade erythrocytes to provide an environment for self-replication and survival. For invasion to occur, the parasite must engage several ligands on the host erythrocyte surface to enable adhesion, tight junction formation and entry. Critical interactions include binding of erythrocyte binding-like ligands and reticulocyte binding-like homologues (Rhs) to the surface of the host erythrocyte. The reticulocyte binding-like homologue 5 (Rh5) is the only member of this family that is essential for invasion and it binds to the basigin host receptor. The essential nature of Rh5 makes it an important vaccine target, however to date, Rh5 has not been targeted by small molecule intervention. Here, we describe the development of a high-throughput screening assay to identify small molecules which interfere with the Rh5-basigin interaction. To validate the utility of this assay we screened a known drug library and the Medicines for Malaria Box and demonstrated the reproducibility and robustness of the assay for high-throughput screening purposes. The screen of the known drug library identified the known leukotriene antagonist, pranlukast. We used pranlukast as a model inhibitor in a post screening evaluation cascade. We procured and synthesised analogues of pranlukast to assist in the hit confirmation process and show which structural moieties of pranlukast attenuate the Rh5 - basigin interaction. Evaluation of pranlukast analogues against P. falciparum in a viability assay and a schizont rupture assay show the parasite activity was not consistent with the biochemical inhibition of Rh5, questioning the developability of pranlukast as an antimalarial. The high-throughput assay developed from this work has the capacity to screen large collections of small molecules to discover inhibitors of P. falciparum Rh5 for future development of invasion inhibitory antimalarials.
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PMID:Development and application of a high-throughput screening assay for identification of small molecule inhibitors of the P. falciparum reticulocyte binding-like homologue 5 protein. 3315 23

COVID-19 has caused significant morbidity and mortality, and new cases are on the rise globally, yet malaria-endemic areas report statistically significant lower incidences. We identified potential shared targets for an immune response to SARS-CoV-2 by immune determinants shared identities with Plasmodium falciparum using IEDB's Immune browser tool 9.0. Probable cross-reactivity is suggested through HLA-A*02:01 and subsequent CD8+ T cell activation. The apparent immunodominant epitope conservation between SARS-COV-2 (N and Orf1ab) and P. falciparum thrombospondin-anonymous-related protein (TRAP) may underlie the low COVID-19 incidence in the malaria-endemic zone by providing immunity against virus infection to those previously infected with plasmodium. Additionally, the shared epitopes lie within antigens which aid in the establishment of the P. falciparum invasion to the erythrocytes may hypothesize an alternative route for SARS-CoV-2, though yet to be proven, via erythrocyte CD147 receptor.
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PMID:SARS-COV2 and P. falciparum common immunodominant regions may explain low COVID-19 incidence in the malaria-endemic belt. 3323 Apr 17


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