Computational Interrogation of The Human Norovirus-Host Cell Interactions Facilitated by A-Type Antigen

Norovirus infectivity, which causes norovirus-induced gastroenteritis, depends on the interaction between capsid protein VP1 of the virus and host cell HGBA receptors that tailor the cell membrane surface. The interaction results in VP1-HGBA complex formation prior to infection. The details of this interaction have been provided by x-ray structures of HGBA-VP1 complexes, but the dynamic nature of this interaction is not fully uncovered. Therefore, the dynamics that drive the formation of VP1-HGBA complex, which is crucial for developing new therapeutic approaches to find a cure for gastroenteritis disease, need to be elucidated. Here, we computationally analyzed the wild type VP1 capsid protein in complex with A-type HGBA antigen to unravel interactions that are important for virus to enter inside the host cell during infection. We have found that the ligand binding causes a fluctuation in a distant loop which resides in the interface of capsid building blocks, VP proteins. This fluctuation leads an instability in capsid particle that may be an indication for virus uncoating mechanism during the cell penetration.