— Research
Seeing is Understanding
For the first few months of the pandemic, SARS-CoV-2 was called simply “the novel coronavirus.” “Novel,” meaning scientists hadn’t seen it before
For the first few months of the pandemic, SARS-CoV-2 was called simply “the novel coronavirus,” “novel,” meaning scientists hadn’t seen it before. And yet the ability to see — really see, at the atomic level — what a microbe looks like and how it interacts with human cells is crucial in helping researchers design better methods to prevent or disrupt those interactions.
Rommie E. Amaro, PhD, professor in the UC San Diego Department of Chemistry & Biochemistry, and collaborators, were among the first to get a close look. They created models of the virus and its interactions with human cells, based on structural data generated from cryo-electron tomography and cryo-electron microscopy — leading-edge techniques that allow researchers to glimpse molecular structures at unprecedented resolution — and a combination of computer modeling and molecular dynamics simulations.
The models revealed a trove of information. For example, SARS-CoV-2’s infamous spike protein, protrusions that help it grab hold of human cells, is coated in sugar molecules known as glycans. These glycans change the spike protein’s shape — important information for researchers trying to target it with new drugs, or drum up antibodies against it with vaccines.
THE VIRUS. The spike proteins protruding from the virus’ spherical lipid bilayer are shown in gray, with glycans highlighted in dark blue.
The spike protein. This is the SARS-CoV-2’s spike protein in its open state. The spike protein is shown in cyan and the sugars forming a so-called “glycan shield” are depicted in dark blue. The spike is embedded in the viral membrane, shown at the bottom as multicolored carpeting.
The infection. SARS-CoV-2 (top) latches onto the ACE-2 receptor (yellow), a molecule on the surface of human cells that the virus uses like a doorknob to gain entry and establish infection.
A. THE VIRUS
Image credit: Lorenzo Casalino
Modeling credit: Abigail C. Dommer, Lorenzo Casalino
Zied Gaieb, Rommie E. Amaro
B. THE SPIKE PROTEIN
Image credit: Lorenzo Casalino
Modeling credit: Lorenzo Casalino, Zied Gaieb, Rommie E. Amaro
C. THE INFECTION
Image credit: Lorenzo Casalino
Modeling credit: Lorenzo Casalino, Abigail C. Dommer Zied Gaieb, Emilia P. Barros, Rommie E. Amaro