Cone snail venom could potentially treat severe forms of malaria

Severe forms of malaria such as Plasmodium falciparum can be fatal even after treatment with current antiparasitic drugs. This is due to a persistent cyto-adhesion of the infected erythrocytes even though the parasites existing in the red blood cells have died.

Malaria vaccines have been shown to be less than moderately effective and in treating these severe cases of P. falciparum malaria, new pathways are urgently needed. Latest estimates indicate that over 500 million malaria cases and over 400,000 deaths are reported worldwide each year. Anti-stick drugs may be the key to significantly improving survival rates.

Using the venom of Conus nux, a species of sea snail, an unpublished study by the Schmidt College of Medicine at Florida Atlantic University in collaboration with the Charles E. Schmidt College of Science at FAU and the Division of Chemical Sciences, National Institute of Standard and Technology , United States Department of Commerce, suggests that these conotoxins could potentially treat malaria.

The study provides important avenues for the development of innovative and cost-effective anti-adhesion or blocking therapy pharmaceuticals aimed at countering severe malaria pathology.

Results, published in the Newspaper proteomics, to extend the pharmacological scope of conotoxins / conopeptides by revealing their ability to disrupt protein-protein and protein-polysaccharide interactions that directly contribute to disease.

Likewise, the mitigation of emerging diseases like AIDS and COVID-19 could also benefit from conotoxins as potential inhibitors of protein-protein interactions as a treatment. The poisonous peptides from conical snails have the potential to treat countless diseases using blocking therapies.

Molecular stability, small size, solubility, intravenous administration, and lack of immunogenic response make conotoxins excellent candidates for blocking therapy. Conotoxins have been studied vigorously for decades as molecular probes and conductors of drugs targeting the central nervous system. They should also be explored for new applications aimed at counteracting poor cellular responses or at thwarting host parasitic interactions by their binding with endogenous and exogenous proteins.

Further research is likely to lead to breakthroughs in areas that continually struggle for more effective therapeutic approaches such as cancer, autoimmune diseases, new emerging viral diseases as well as malaria where natural peptide-based products. of venom can be put into practice. “

Andrew V. Oleinikov, Ph.D., corresponding study author and professor of biomedical sciences, Schmidt College of Medicine, Florida Atlantic University

The disruption of protein-protein interactions by conotoxins is an extension of their well-known inhibitory action in many ionic channels and receptors. Disabling prey by specifically modulating their central nervous system is a guiding principle in the mode of action of venoms.

“Among the more than 850 species of conical snails, there are hundreds of thousands of diverse venomous exopeptides which have been selected over millions of years of evolution to capture their prey and deter predators,” said Frank Marí, Ph.D., Corresponding Author and Senior Advisor for Biochemical Sciences at the National Institute of Standard Technology. “They do this by targeting several surface proteins present in the target excitable cells. This huge biomolecular library of conopeptides can be explored for potential use as therapeutic avenues against persistent and emerging diseases affecting non-excitable systems.”

For the study, the researchers used high-throughput tests to study Conus nux collected off the Pacific coast of Costa Rica. They revealed the in vitro ability of conical snail venom to disrupt protein-protein and protein-polysaccharide interactions that directly contribute to pathology of P. falciparum malaria. They determined that six fractions of the venom inhibited the adhesion of recombinant P. falciparum the erythrocyte membrane protein 1 (PfEMP-1) domains at their corresponding receptors, which are expressed on endothelial microvascularization and the placenta.

The results are remarkable because each of these six venom fractions, which contain a predominantly unique or very limited set of peptides, affected the binding of domains with different receptor specificity to their corresponding receptors, which are proteins (CD36 and ICAM -1), and polysaccharide.

This activity profile suggests that the peptides in these conotoxin moieties bind to common structural elements in the different PfEMP1 domains, or that a few different peptides in the moiety may interact effectively (the concentration of each is proportionately less than the complexity) with different areas.