In silico Discovery of Leptukalins, The New Potassium Channel Blockers from the Iranian Scorpion, Hemiscorpius Lepturus

Background: Blocking Kv 1.2 and Kv 1.3 potassium channels using scorpion venom-derived toxins holds potential therapeutic value. These channels are implicated in autoimmune diseases such as and type 1 diabetes. Objective: The present work aims at the discovery and in silico activity analysis of potassium channel blockers (KTxs) from the cDNA library derived from the venom gland of Iranian scorpion Hemiscorpius lepturus (H. lepturus) Methods: The sequence regarding potassium channel blockers were extracted based on Gene Ontology for H. lepturus venom gland. Homology analyses superfamily family and evolutionary signatures of H. lepturus KTxs (H.L KTxs) were determined by using BLASTP COBALT PROSITE and InterPro servers. The predicted 3D structures of H.L KTxs were superimposed against their homologs to predict structure activity relationship. Molecular docking analysis was also performed to predict the binding affinity of H.L KTxs to Kv 1.2 and Kv 1.3 channels. Finally the toxicity was predicted. Results: Seven H.L KTxs designated as Leptukalin were extracted from the cDNA library of H. lepturus venom gland. Homology analyses proved that they can act as potassium channel blockers and they belong to the superfamily and family of Scorpion Toxin-like and Short-chain scorpion toxins respectively. Structural alignment results confirmed the activity of H.L KTxs. Binding affinity of all H.L KTxs to Kv 1.2 and Kv 1.3 channels ranged from -4.4 to -5.5 and -4 to -5.7 Kcal/mol respectively. In silico toxicity assay showed that Leptukalin 3 Leptukalin 5 and Leptukalin 7 were non-toxic. Conclusion: Three non-toxic KTxs Leptukalin 3 5 and 7 were successfully discovered from the cDNA library of H. lepturus venom gland. Gathering all data together the discovered peptides are promising potassium channel blockers. Accordingly Leptukalin 3 5 and 7 could be suggested for complementary in vitro studies and mouse model of autoimmune diseases.