Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.
Unexplained fever poses significant diagnostic challenges in resource-limited settings like Bamako, Mali, where overlapping endemic diseases include malaria, HIV/AIDS, yellow fever, typhoid, and others. This study aimed to elucidate the infectious etiologies of acute febrile illnesses in this context. Acute febrile patients of any age were enrolled after informed consent or assent.
Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria; College of Health Sciences, Osun State University, Osogbo, Osun State, Nigeria.
Cerebral malaria (CM) is a fatal complication of Plasmodium falciparum infection. The biological and physiological links between CM, inflammation, and inflammasome, point to the complexity of its pathology. Resistance to available and affordable drugs, worsening economic crisis, and urgent need for integration of orthodox with traditional/alternative medicine, actualized the search for sustainable pharmacotherapy.
Introduction: Malaria remains a significant burden, and a fully protective vaccine against is critical for reducing morbidity and mortality. Antibody responses against the blood-stage antigen Merozoite Surface Protein 2 (MSP2) are associated with protection from malaria, but its extensive polymorphism is a barrier to its development as a vaccine candidate. New tools, such as long-read sequencing and accurate protein structure modelling allow us to study the genetic diversity and immune responses towards antigens from clinical isolates with unprecedented detail.
Background: Molecular methods play an important role in clinical trials assessing anti-malarial drugs and vaccines, as well as in epidemiological studies aimed at detecting Plasmodium species, especially when dealing with large sample sizes. Molecular techniques are more sensitive and generally have a higher throughput compared to the gold standard microscopy. Further optimization can be achieved with automation of nucleic acid isolation, allowing for rapid and precise extraction.
Essential genes are those whose presence is vital for a cell's survival and growth. Detecting these genes in disease-causing organisms is critical for various biological studies, including understanding microbe metabolism, engineering genetically modified microorganisms, and identifying targets for treatment. When essential genes are expressed, they give rise to essential proteins.
