Understanding COVID-19’s Evolutionary Journey through Spike Protein Structural Analysis

A team at the Francis Crick Institute successfully characterized the structure of the SARS-CoV-2 spike proteins. While the evolutionary journey that gave the virus its ability to infect humans is not fully known, this information could help vaccine development and design. 

The study published in Nature Structural & Molecular Biology details how the team observed the spike proteins in high resolution using cryo-electron microscopy. They then compared SARS-CoV-2’s protein structures with those of a bat coronavirus, RaTG13. 

While mostly similar, the differences found mean that the spikes of SARS-CoV-2 are more stable and able to bind 1,000 more tightly to a human cell than the bat virus. The most significant varying factor involved the location of where the virus binds with the ACE2 receptor in human cells. 

"The spike is the entry key that allows SARS-CoV-2 into human cells. Changes in the virus' genome, which affect the spike's structure, therefore have the potential to make the virus either more or less able to enter the host's cell," says Antoni Wrobel, co-lead author. 

"At some point in the evolution of this virus, it seems to have picked up changes, like the differences we found, which made it able to infect humans,” Wrobel adds. Based on their results, the team suggests its unlikely that a virus similar to RaTG13 could infect human cells, supporting the theory that SARS-CoV-2 could be the result of different coronaviruses evolving together over time, and possibly through different hosts. 

The spike protein structures are open-access with the hope that other researchers will use their work to aid drug discovery and vaccine design. "The world was caught off guard by SARS-CoV-2. Examining the structure of this virus, and its likely precursor, helps us understand where it came from, and how it interacts with human cells," co-author Steve Gamblin adds.