Human (h) coronaviruses (CoVs) 229E, NL63, OC43, and HKU1 are less virulent and cause mild, self-limiting respiratory tract infections, while SARS-CoV MESHD
, MERS-CoV, and SARS-CoV-2, are more virulent and have caused severe outbreaks. The CoV envelope (E) protein PROTEIN
, an important contributor to the pathogenesis of severe hCoVs infections MESHD
, may provide insight into this disparate severity of the disease. Topology prediction programs and 3D modelling software was used to predict and visualize structural aspects of the hCoV E protein PROTEIN
related to its functions. All seven hCoV E proteins PROTEIN
largely adopted different topologies, with some distinction between the more virulent and less virulent ones. The 3D models refined this distinction, showing the PDZ-binding motif (PBM) of SARS-CoV MESHD
, MERS-CoV, and SARS-CoV-2 to be more flexible than the PBM of hCoVs 229E, NL63, OC43, and HKU1. We speculate that the increased flexibility of the PBM may provide the more virulent hCoVs with a greater degree of freedom, which can allow them to bind to different host proteins and can contribute to a more severe form of the disease. This is the first paper to predict the topologies and model 3D structures of all seven hCoVs E proteins PROTEIN
, providing novel insights for possible drug and/or vaccine development.