Identification of Potential Insulinotropic Cytotoxins from Indian Cobra Snake Venom Using High-Resolution Mass Spectrometry and Analyzing Their Possible Interactions with Potassium Channel Receptors by In Silico Studies.

Snake venoms are a potential source of bioactive peptides, which have multiple therapeutic properties in treating diseases such as diabetes, cancer, and neurological disorders. Among bioactive peptides, cytotoxins (CTXs) and neurotoxins are low molecular weight proteins belonging to the three-finger-fold toxins (3FTxs) family composed of two ß sheets that are stabilized by four to five conserved disulfide bonds containing 58-72 amino acid residues. These are highly abundant in snake venom and are predicted to have insulinotropic activities. In this study, the CTXs were purified from Indian cobra snake venom using preparative HPLC and characterized using high-resolution mass spectrometry (HRMS) TOF-MS/MS. Further SDS-PAGE analysis confirmed the presence of low molecular weight cytotoxic proteins. The CTXs in fractions A and B exhibited dose-dependent insulinotropic activity from 0.001 to 10 µM using rat pancreatic beta-cell lines (RIN-5F) in the ELISA. Nateglinide and repaglinide are synthetic small-molecule drugs that control sugar levels in the blood in type 2 diabetes, which were used as a positive control in ELISA. Concluded that purified CTXs have insulinotropic activity, and there is a scope to use these proteins as small molecules to stimulate insulinotropic activities. At this stage, the focus is on the efficiency of the cytotoxins to induce insulin. Additional work is ongoing on animal models to see the extent of the beneficial effects and efficiency to cure diabetes using streptozotocin-induced models.

Pre-clinical assessment of the effectiveness of modified polyvalent antivenom in the neutralization of Naja naja venom toxicity.

The potency of conventional antivenom (AV) conjugated to soy protein nanoparticles (NPs) (C-AV) was compared with the free AV in neutralizing the systemic toxicity of Naja naja venom. The effective dose (ED50 ) of AV and C-AV to neutralize the venom-induced toxicity in mice was found to be 19.89 and 9.50 mg, respectively. The histopathological examination of heart, liver, and kidney indicated that the systemic toxicity induced by the venom was effectively neutralized by lower concentrations of C-AV than compared with AV. In addition, C-AV was found to be more effective in neutralizing the edema forming activity of N. naja venom compared with the AV. Thus, the results of this study indicate that the potency of commercially available AV could be improved by conjugating it to soy protein NPs.