COMPUTATIONAL MODELING OF SOLUPLUS® NANOMICELLES AND IgG INTERACTIONS: A POTENTIAL APPROACH FOR TARGETING SHIGA TOXIN TYPE 2 AND PREVENT HEMOLYTIC UREMIC SYNDROME

CASAL, JUAN J.; GIRÓN REYES, CLAUDIO D.; AMARAL, MARÍA M.; SACERDOTI, FLAVIA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias 2023; 2023

Sociedad Argentina de Investigación Clínica (SAIC), la Sociedad Argentina de Biología (SAB), la Asociación Argentina de Farmacología Experimental (AAFE) y la Asociación Argentina de Ciencia y Tecnología de Animales de Laboratorio (AACYTAL)

Shiga toxin type 2 (Stx2) is secreted by Shiga toxin producing Escherichia coli during infection and is responsible for developing Hemolytic Uremic Syndrome (HUS), a systemic disease characterized by hemolytic anemia, thrombocytopenia and acute kidney injury. Nowadays, there is no specific treatment available for HUS. Soluplus® is an amphiphilic polymer that spontaneously assembles in nanomicelles (NM) in aqueous solutions and is commonly used for solubilization and dministration of poorly soluble drugs. We propose that Soluplus® nanomicelles associated with anti Stx2 IgG may improve IgG properties of toxin neutralization and propose them as a treatment for HUS. In this study we aimed to investigate potential interactions between Soluplus® and IgG by computational modeling to better understand the association between both molecules. For that, the crystal structure of Soluplus® was designed using Marvin Chemsketch 23.10, based on information from the manufacturer. A reduced version of Soluplus® was generated, preserving the monomer proportions and resulting in a molecule with a molecular weight of 42 kDa. Docking calculations were performed using AutoDock Vina 1.2.5 with the IgG antibody (PDB code 1IGY) as the model protein. The search box, centered on amino acid GLY236 of the B chain, had dimensions of 126 Å in each direction (x, y, z). The docking results were analyzed based on the scoring function, which implicitly incorporated the solvent effect. The pose with the lowest binding energy was selected for further analysis. Interactions between Soluplus® and the IgG antibody were examined using LigPlot+ 2.2.8. Our computational modeling indicates that Soluplus® interacts with IgG mostly by the Fc portion of the antibody, thus suggesting that IgG may perform a corona in the nanomicelles and give a better solubilization of the IgG in aqueous solutions. These results are in concordance with the biological studies that indicate that NM improve the neutralization capacity of anti Stx2 IgG in vitro, suggesting that coupling IgG to Soluplus® could be a potential strategy to prevent HUS.