A potent neuropeptide from venom gland of Iranian scorpion, Mesobuthus crucittii: Characterization and insights into its potential biological function

Scorpion venom is an amazing source to find pharmacological peptides to treat wide range of diseases. However, few studies are going through the clinical phases, and no scorpion peptide has yet been approved by the FDA for general prescription. Therefore, the scorpion venom gland can be a special opportunity to find effective, selective, and targeted medicinal peptides. Here we analyzed the transcriptome of an Iranian scorpion, Mesobuthus crucittii, to find and characterize a pharmacological potent peptide. transcriptome obtained from RNA-sequencing was analyses using Blast to find similar peptides to intended peptide. physicochemical properties of the peptide were determined using Protparam and PepCalc web servers Three-dimensional structure of the peptide was predicted using Swiss-model. Helical Wheel Projection of the peptide was draw to determine its amphipathicity. Its mechanism of action on physiological conditions and its therapeutic effects were discussed and evaluated based on sequence similarity analysis. We identified a water-soluble ۱۴۵ amino acid peptide from venom gland of M. crucittii with molecular weight of ۱۷۲۰۲ g/mol. This peptide was submitted at GenBank under the name, meuVNP۲. Structure of this peptide is composed two alpha-helixes. Analysis of Helical Wheel Projection of meuVNP۲ shows the alpha-helix of this peptide is amphipathic. This peptide exhibits a conserved Orcokinin-like motif (NFDEIDR) which is important for its activity, suggesting a dual role for this peptide, both endogenous neuromodulator and as a venom component. Identification of meuVNP۲ suggests its potential as a structural template for the development of neuroactive therapeutics. Given its similarity to Orcokinin, meuVNP۲ may increase intestinal motility with activating enteric neurons and modulating parasympathetic signals. It may also enhance the heart rate by directly stimulating pacemaker cells or cardiac receptors, and strengthen cardiac contractions through GPCR-mediated calcium channel regulation. So, meuVNP۲ can be as a promising candidate for the development of drugs which target gastrointestinal motility disorders and mild forms of heart failure.

کلیدواژه ها:

Scorpion venom peptide ، Drug development ، Iranian scorpion ، Biological molecules