Scientists at the US Department of Energy’s Brookhaven National Laboratory have published the first detailed model of a protein on the surface of the coronavirus envelope that interacts with a key protein in human lung cells. The results of the study, published in the journal Nature Communications, helped to unravel the reason why SARS-CoV-2 can cause deadly damage to the respiratory and other organs.
To develop a molecular model, the scientists used a cryo-electron microscope at the Laboratory of Biomolecular Structure (LBMS). Cryoelectron microscopy is suitable for studying membrane proteins and dynamic protein complexes, from which it is difficult to obtain crystals for crystallography, and also allows you to trace the dynamics of molecules.
The E envelope protein is located on the outer surface of the virus and, along with the spike protein, helps the virus to enter the cell and further replicate. It also plays a critical role in intercepting human proteins to facilitate the release and transmission of the virus to other cells. It is assumed that it does this through binding to the surface proteins of PALS1, disrupting the tight adhesion of cells to each other.
As the contacts between lung cells are disrupted, immune cells try to repair the damage by releasing cytokines. This immune response can exacerbate the situation, causing systemic inflammation, the so-called “cytokine storm” and subsequent acute respiratory distress syndrome. The weakening of cell-cell communication allows viruses to more easily leave the lungs and enter the bloodstream to infect other organs, including the liver, kidneys, and blood vessels.