Computational characterization of HIV envelope interactions with cellular GRP78 as a potential entry mechanism

Human Immuno-deficiency virus (HIV) is still spreading all over the world. There are many routes through which the virus recognizes host cells by its envelope protein. One of these routes is through binding to glucose-regulated protein 78 (GRP78), which is overexpressed in stressed cells. In this study, we investigate the association between GRP78 and HIV envelope protein at four different binding sites (R1: C130-C162), (R2: C223-C252), (R3: C301-C335), and (R4: C388-C418) using a comprehensive in silico approach. Protein-protein docking and molecular dynamics simulations (MDS) are conducted to evaluate the binding. Results indicate that the R4 region (C388-C418) is the potential binding site of the envelope protein to GRP78 on the cell surface with an average binding energy of -12.20 ± 2.0 kcal/mol. The predicted findings open the gate towards further studies that could lead to the development of effective inhibitors that can alleviate viral recognition of the host cell and eradicate the viral infection.