Investigating the Binding Efficacy of Snake Venom Proteins as GLP-1 Analogs for Diabetes mellitus Management: An In silico Study

Abstract

Objective: Diabetes mellitus (DM) is a metabolic condition defined by hyperglycemia driven by insulin deficiency or decreased insulin activity. GLP-1, a gut enzyme, stimulates insulin production and reduces hepatic glucose synthesis to regulate diabetes. GLP-1 agonists enhance insulin sensitivity and decrease blood glucose to relieve symptoms of DM. These medications represent a novel paradigm to manage diabetes as they improve glycaemic control in type 2 diabetic patients. Snake venom proteins have been investigated as a potential medicinal strategy for diabetes treatment. These proteins contain a multitude of bioactive constituents, such as insulinotropic cytotoxins, which have been found to influence insulin secretion and glucose homeostasis. Methods: In the present study, the snake venom proteins long neurotoxin 1 Cytotoxin 7, Cytotoxin 2a, and Cytotoxin 10 were modeled and their therapeutic efficacy as GLP-1 analogs was determined by employing molecular docking techniques. The binding of snake venom protein towards GLP-1 receptors was compared against the positive controls (Exenatide, Liraglutide, Semaglutide, and Lixisenatide). Results: The results demonstrated that the cytotoxins (Cytotoxin 2a, Cytotoxin 7, and Cytotoxin 10) exhibited comparable binding with the positive controls and majorly interacted with the hydrophobic amino acids in the binding pocket of the GLP-1 receptor. The modeled snake venom toxins demonstrated beneficial physicochemical properties and advocated them to be a novel contender for the development of GLP-1 analogs. Conclusion: Despite its beneficial outcomes, the utilization of snake venom proteins as a therapeutic agent for diabetes is still in its initial stages, and additional research is required to assess their effectiveness and safety in patients.