In this study, the molecular docking approach was utilized to assess the effect of 70 flavonoids on the inhibition of glucose-regulated protein 78 kDa (GRP78). Epigallocatechin gallate (EGCG) was employed for the selection of the studied flavonoids based on estimated binding energy. Four compounds, namely, naringin, poncirin, prunin, and epicatechin gallate showed higher affinities to GRP78. The predicted binding energy for these compounds was respectively − 11.60, − 10.40, − 10.19 and − 10.04 (kcal/mol) in comparison with the value of − 9.86 (kcal/mol) for EGCG. The hydrogen bond with residues Asp391, Gly228, Thr229, Glu256, and Lys296, and hydrophobic interactions with Tyr39, Ile61, Gly226, Gly227, Glu293, Lys296, Gly363, Gly364, and Asp391 residues are the major interactions between candidate flavonoids and GRP78 receptor. It can be concluded that some flavonoids interfered with the main residues within the ATPase domain to inhibit GRP78.
