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