Assessing the Viability of Peginterferon Alfa-2b Inhibiting Neurotoxin-Ganglioside Binding in Guillain-Barré Syndrome

Abstract

Guillain-Barré Syndrome (GBS) is a debilitating neurological condition causing damage to the neural plasticity across the peripheral nervous system from an autoimmune response triggered by the binding of pathogen-derived neurotoxins to glycosphingolipid carriers being gangliosides. Though current treatment solely targets such a response post-onset through intravenous immunoglobulin infusion, an approach to suppressing the initial exhibition of GBS derives from ceasing neurotoxins from attachment to gangliosides through administering Peginterferon Alfa-2b, an immunomodulatory drug, as a ligand to attach and block to binding domain proteins to restrict neurotoxin-ganglioside contiguity. Through in-silico docking, a protein-ligand complex was manufactured amongst Peginterferon Alfa-2b and Clostridium botulinum neurotoxin protein 8AGK, a binding domain known for attachment to GD1a gangliosides. This analyzed the viability in administration and affinity of the Peginterferon ligand in blocking 8AGK’s ganglioside-binding capabilities as a feasible primary therapy against this critical syndrome. Assessing binding strength was evaluated by measuring statistical variations in mean distances for components vital to the binding affinity for the Peginterferon including Angstroms between optimal and computed hydrophobic overlapping and hydrogen bonding interactions amongst protein-ligand residues. Furthermore, the bioavailability, lipophilicity, solubility, and chemistry of the Peginterferon using SwissADME were assessed for feasibility in real-world therapeutic applications. Through evaluating such components, results demonstrated that Peginterferon Alfa-2b was effective as a pharmaceutical to combat GBS for its strong binding affinity of maximizing Van der Waals contacts whilst minimizing steric hindrance coupled with desirable pharmacokinetics for real-world application. Such findings underscore the potential for a novel, proactive approach to treating GBS.