Coralyne induced disintegration of lysozyme fibrillar aggregates: A spectroscopic, microscopic and theoretical...

Amyloid fibril formation by misfolded proteins is the hallmark of several neurodegenerative disorders. Although numerous small molecules have been reported to inhibit fibrillogenesis but recent strategies have been targeted towards disassembling preformed fibrils. So in the present study we have evaluated the ability of Coralyne (COR), a protoberberine alkaloid, to disaggregate preformed fibrils in Hen Egg White Lysozyme (HEWL). Thioflavin T (ThT) fluorescence assay demonstrated quantitatively the fibril destabilization capability of COR. Nile red (NR) and 8-Anilinonaphthalene-1-sulphonic acid (ANS) binding assay revealed a significant hydrophobic surface exposure change due to presence of COR which was consistent with disruption of fibrillar core. Far-UV circular dichroism spectroscopy (CD) confirmed the loss of β sheet secondary structure on COR treatment. Atomic Force Microscopy (AFM) provided direct morphological evidence of fibril fragmentation and reduced height distribution. Furthermore molecular docking analysis identified probable binding mechanism of COR with HEWL fibrillar assemblies and revealed the key non-covalent interactions underlying its activity. Collectively these findings establish COR as a potent defibrillating agent and underscore its potential as a lead scaffold for therapeutic intervention targeting amyloid clearance.