Human lysozyme and several of its familial mutants form amyloid fibrils and are responsible for systemic amyloidosis affecting liver and kidney.It is known that destabilization of the native protein structure is responsible for the formation of intermediate species prone to fibril formation.It is, therefore, important to design strategies for stabilization of the lysozyme structure either by using known protein structure stabilizers like osmolytes or by using small molecules that could directly bind to the protein and act as inhibitors of aggregation.Some polyphenols have recently been shown to inhibit aggregation of Aβ and α-synuclein involved in neurodegenerative diseases.In this study we probed the effect of red wine polyphenol reseveratrol on the fibril formation pathway of human lysozyme at pH 7.4 and 2.There was significant suppression of fibril formation at concentrations as low as 100 μM resveratrol as probed by thiofiavin-T binding assay.The findings were supported by electron microscopy and DLS studies.The hydrophobic groups of the protein were also less exposed to solvent in the presence of resveratrol as probed by ANS binding which was supported by DSC measurements showing greater stability of the protein in resveratrol as a result of increasing thermal transition temperature.Fluorescence titration experiments as well as Isothermal titration calorimetry measurements revealed direct binding of resveratrol to lysozyme with a dissociation constant in micromolar range and free energy of binding of-6.8 kcal/mol.It is suggested that strong binding of resveratrol to lysozyme and its structural stabilization is responsible for the suppression of fibril formation and that the presence of resveratrol is required in the earliest phase of fibrillation pathway for effective suppression of amyloid fibrils.