Since the SARS-CoV-2 virus began its global spread, much attention has been focused on the particular group of viruses known as “coronaviruses”. Thus named for the crownlike spikes on their surfaces, these coronaviruses were first identified in the early 1960s and have been responsible for several widespread diseases since. To combat these illnesses, many researchers have begun to examine the most significant shared feature of these viruses – the spike proteins.
What Is a Spike Protein?
All coronaviruses have a “crownlike” (corona) appearance when examined under a microscope. This appearance is the result of numerous spikes protruding from the surface of the virus. These spikes are formed by surface proteins, which have earned the apt name of “spike proteins”.
In COVID-19, as with other coronavirus infections, these spike proteins bind with receptors on the surfaces of victim cells. This first step of infection is a critical moment in the overall disease process. Therefore, a detailed picture of the molecular interactions involved at this point has the potential to lead to breakthroughs in coronavirus treatment and prevention.
Common Roadblocks to Advanced Research
Unfortunately, traditional methods of purifying and isolating spike proteins do not provide information regarding how spike proteins behave within the context of real-life infections. For example, isolating the protein could alter its structure, as it is no longer attached to the virus’s surface. Such structural changes ultimately affect the protein’s function and change its behavior when exposed to a victim cell.
In addition, the COVID-19 virus itself is so virulent that only a few laboratories in the world are equipped to safely study spike proteins while they are still attached to the virus itself. As a result, researchers have begun to explore the study of spike proteins belonging to milder coronaviruses. These proteins bind to human cells in a way that is similar to the COVID-19 virus, attaching to the same set of receptors.
Advanced Techniques Reveal New Information
Using a mild coronavirus strain known as NL63 – a virus that causes the common cold – researchers at Stanford University’s National Accelerator Laboratory were able to flash-freeze an entire virus intact, preserving the spike proteins in their natural state. Repeated virus samples were then photographed in a wide variety of positions and angles using cryo-electron microscopy instruments. Researchers combined the resulting image sets and magnified the spike proteins, resulting in never-before-seen views of these vital proteins’ structures.
Unlike other methodologies that utilized formaldehyde to ward against infectious properties, these spike proteins are unaltered by chemicals. The team was able to identify sites on the protein where sugar molecules attach, confirming previously-hypothesized glycosylation sites. These sites are a critical component of a virus’s ability to ward off advances by the immune system and may reveal important information necessary to fight their infectious abilities.
Optimization of this new methodology could critically impact the scientific community’s ability to analyze COVID-19’s spike protein structure. Although studies on similar coronaviruses are useful, researchers hope to perform the same techniques on COVID-19 spike proteins on the virus’s surface in specialized labs. Eventually, it is hoped that further study will reveal the mechanisms by which the COVID-19 spike protein binds with victim cells. This crucial information could lead to the development of more effective therapeutic treatments and vaccines.