IN SILICO AND IN VITRO STUDIES TO CHARACTERIZE INHIBITION OF STAPHYLOCOCCAL ENTEROTOXIN B INTERACTIONS WITH HOST CELLS

Abstract

Staphylococcal eneterotoxin B (SEB) is known to form complexes with MHC class II molecules and T-cell receptors. A considerable amount of structural data is now available describing the molecular architecture for SEB and has identified the MHC class II and TCR recognition sites on the toxin molecule. An in silico three dimensional pharmacophore model for inhibition of the formation of SEB-MHC-II complex was created using the CATALYST methodologies. This allowed generation of functional attributes of molecules to develop the pharmacophore model for specific biological activity. Using the conformational thermodynamics of potential compounds along with other molecular properties such as favorable ADME, 36 potential inhibitors for SEBMHC-II binding were identified. These selected compounds were tested using in vitro toxin binding and proliferation assays. 3 compounds were identified that demonstrated inhibition of the SEB-MHC-II-TCR complex formation.