The interactions ofVP37 protein from white spot syndrome virus with glycosaminoglycan according to the sulfate content

The crystal structure of the C-terminal domain of protein VP37 fromthe White Spot Syndrome Virus(WSSV) was recently reported, revealing sulfate binding sites that are important for heparin binding. However, due to the lack of VP37andheparin complex structure, it remained unclear how the two molecules would interact. Therefore, this study aimed to investigate the interaction between the VP37 protein and heparin, as well as other three different glycosaminoglycans (GAGs) including heparan sulfate,chondroitin sulfate, and hyaluronic acid through molecular docking. The docking results indicated that interactions between VP37 and GAGs occurs at the positively charged patches on top of the VP37 protein. This interaction relies on and is also related to the degree of sulfation on the GAGs molecules. As a result,hyaluronic acid (which lacks sulfates) exhibited an inability to bind to the VP37 protein. The findings were consistent with observed binding energy, with heparin exhibiting the strongest binding energy to VP37(-15.83 kcal/mol), followed by heparan sulfate (-14.30 kcal/mol) and chondroitin sulfate (-11.58 kcal/mol).Furthermore, we identified three amino residuesof VP37that could function as a GAGs binding site, namely K141, T142, and T144 might facilitate the interactions of GAGs at sulfate binding sites on VP37. The data derived from this study can serve as useful for developing antiviral compounds targeting the VP37 to help prevent WSSV infectionin shrimps.