Snail pox poison shows ability to treat severe malaria

Severe forms of malaria such as Plasmodium falciparum can be fatal even after treatment with conventional parasite killing drugs. This is due to persistent cyto-adhesion of infectious erythrocytes even though existing parasites within the red blood cells are dead. Because vaccines for malaria have not been as effective as effective, and to address these severe cases of P. falciparum malaria, new pathways are needed immediately. The latest estimates show that more than 500 million cases of malaria and more than 400,000 deaths are reported worldwide each year. Anti-adhesion drugs may be a key way to significantly improve survival rates.

Using poison from the Conus nux, a species of sea snail, a first-class study from Florida Atlantic University’s Schmidt College of Medicine in collaboration with FAU’s Charles E. Schmidt College of Science and Department of Chemical Sciences, National Institute of Standard and Technology, United States Department of Commerce, suggests that these conotoxins may treat malaria. The study provides important directions towards the development of novel and cost-effective anti-adhesion medications or blockade-therapy aimed at combating the pathology of malignant malaria.

Results, published in the Iris de Proteomics, expanded the pharmacological availability of conotoxins / conopeptides by demonstrating the ability to inhibit protein-protein and protein-polysaccharide interactions that directly contribute to the disease. Similarly, mitigation of emerging diseases such as AIDS and COVID-19 may also benefit from conotoxins as potential inhibitors of protein-protein interactions as a treatment. Venom peptides from cone snails have the ability to treat innumerable diseases using preventive therapies.

“Molecular stability, small size, flexibility, intravenous delivery, and no immunogenic response make candidates excellent blockade-therapy conotoxins,” said Andrew V. Oleinikov, Ph.D., associate author and professor of science biochemical, Schmidt College of Medicine FAU. “Conotoxins have been strongly studied for decades as molecular probes and drug drivers targeting the central nervous systems. They should also be studied for novel applications aimed at inhibiting amiss cellular responses or the elimination of host parasite interactions by binding to endogenous and exogenous proteins Further study is likely to cause disruption in areas of continuous thatching for therapeutic approaches more effective such as cancer, autoimmune diseases, emerging viral diseases as well as malaria where natural peptidic products based on poisons can be applied. ”

The interaction of protein-proteins with conotoxins is an extension of their well-known inhibitory action in many ion channels and receptors. Eliminating prey by altering their nervous system in particular is a governing principle in the mode of action of toxins.

“More than 850 species of cone snails include hundreds of thousands of miscellaneous poisonous exopeptides selected through several million years of evolution to capture their prey and deter predators,” said Frank Marí, Ph.D., associate author and senior consultant for biochemical sciences at the National Institute of General Technology. “They do so by targeting several surface proteins present in excitable target cells. This large biomolecular library of conopeptides can be studied for use as therapeutic guidelines against chronic and developing diseases. emerges that affect non-restrictive systems. ”

For the study, researchers used high-throughput assays to study Conus nux collected off the Pacific coast of Costa Rica. They demonstrated the in vitro ability of cone snail poison to inhibit protein-protein and protein-polysaccharide interactions that directly contribute to P. falciparum malaria pathology. They concluded that six fractions of the toxin inhibit the cleavage of the P. falciparum erythrocyte membrane 1 (PfEMP-1) regenerative domains to their corresponding receptors, which are on the endothelial microvasculature and the placenta.

The results are noteworthy as each of the six toxin fractions, consisting mainly or very little of a set of peptides, is associated with a link between domains with different receptor specificity and the co-receptors. corresponding to them, which are proteins (CD36 and ICAM-1), and polysaccharide. This activity profile suggests that the peptides in these conotoxin fractions either bind to common structural elements in the different PfEMP1 regions, or that several different peptides in the proportion may interact to h -efficient (the density of each is lower depending on the complexity) with different ranges.

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Co-study authors Alberto Padilla, Ph.D., first author and graduate student, Schmidt College of Medicine FAU; Sanaz Dovell, Ph.D., who was a student at the Charles E. Schmidt College of Science at FAU; Olga Chesnokov, Ph.D., research associate, FAU Schmidt College of Medicine; and Mickelene Hoggard, Ph.D., Department of Chemical Sciences, National Institute of Standards and Technology.

This research is supported in part by the National Institute of Allergies and Infectious Diseases (grants R21A137721 and R01AI092120) awarded to Oleinikov.

Charles E. Schmidt College of Medicine at FAU is one of approximately 155 accredited medical schools in the U.S. The college was launched in 2010, when the Florida Board of Governors made a special decision authorizing FAU’s provide an MD degree. After receiving approval from the Florida legislature and the governor, it became the 134th allopathic medical school in North America. With more than 70 full-time and part-time faculties and more than 1,300 affiliated faculties, the college matrics 64 medical students each year and is nationally recognized for its innovative curriculum. To build on FAU ‘s commitment to increasing much – needed medical residency in Palm Beach County and to ensure that the area has an appropriate and well – trained physician staff, the Charles E. Schmidt College of Medicine Consortium FAU to establish Graduate Medical Education (GME) in fall 2011 with five major hospitals in Palm Beach County. The Consortium for Graduate Medical Education (ACGME) currently has five accredited residences covering inpatient medicine, surgery, emergency medicine, psychiatry and neurology.

Florida Atlantic University, founded in 1961, officially opened its doors in 1964 as the fifth public university in Florida. Today, the University serves more than 30,000 undergraduate and graduate students across six campuses located on the southeast coast of Florida. In the last few years, the University has doubled its research costs and outperformed its peers in student achievement levels. Through a combination of accessibility and excellence, FAU introduces an innovative model where traditional performance gaps are closing. FAU is designated as a Hispanic-serving center, regarded as a leading public university by US News & World Report and a Carnegie Foundation-based Advanced Research Activity institute for Teaching Advancement. For more information, visit http: // www.fau.edu.