The emergence of a new variant of coronavirus has sparked renewed interest in the part of the virus known as the spike protein. The new variant carries several peculiar changes in the spike protein compared to other closely related variants, and that is one reason why it is more of a concern than other harmless changes in the virus that we have observed before.
The new mutations can alter the biochemistry of the peak and affect the transmission of the virus. The spike protein is also the basis of current COVID-19 vaccines, which seek to generate an immune response against it. But what exactly is spike protein and why is it so important?
In the world of parasites, many bacterial or fungal pathogens can survive on their own without a host cell to infect. But viruses can’t. Instead, they have to enter cells to replicate, where they use the cell’s own biochemical machinery to build new virus particles and spread to other cells or individuals.
Our cells have evolved to protect themselves from these intrusions. One of the main defences that cell life has against invaders is its outer coating, which is made up of a fatty layer that contains all the enzymes, proteins and DNA that make up a cell. Due to the biochemical nature of fats, the outer surface is highly negatively charged and repellent. Viruses must cross this barrier to enter the cell.
Like cellular life, coronaviruses themselves are surrounded by a fatty membrane known as an envelope. In order to enter the interior of the cell, enveloped viruses use proteins (or glycoproteins, as they are often covered in slippery sugar molecules) to fuse their own membrane with that of the cells and take over the cell. The peak protein of coronaviruses is one of those viral glycoproteins. The Ebola viruses have one, the influenza virus has two, and the herpes simplex virus has five.
The architecture of the pin
The spike protein is made up of a linear chain of 1,273 amino acids, carefully folded into a structure, that is studded with up to 23 sugar molecules. Tip proteins like to bind together and three separate tip molecules bind together to form a “trimeric” functional unit.
The peak can be subdivided into different functional units, known as domains, that fulfil different biochemical functions of the protein, such as binding to the target cell, fusing with the membrane, and allowing the peak to settle into the viral envelope.
The spike protein is made up of different sections that perform different functions. Rohan Bir Singh, CC BY
The SARS-CoV-2 spike protein is attached to the roughly spherical viral particle, embedded within the envelope and projected into space, ready to adhere to unsuspecting cells. It is estimated that there are approximately 26 spiny trimers per virus.
One of these functional units binds to a protein on the surface of our cells called ACE2, which triggers uptake of the virus particle and, ultimately, membrane fusion. The spike is also involved in other processes such as assembly, structural stability, and immune evasion.
Vaccine vs spike protein
Given how crucial spike protein is to the virus, many vaccines or antiviral drugs target viral glycoproteins. For SARS-CoV-2, the vaccines produced by Pfizer / BioNTech and Moderna instruct our immune systems to make our own version of the spike protein, which occurs shortly after immunization. The production of the spike within our cells initiates the process of producing protective antibodies and T cells.
One of the most concerning characteristics of the SARS-CoV-2 spike protein is how it moves or changes over time during the evolution of the virus. Encoded within the viral genome, the protein can mutate and change its biochemical properties as the virus evolves.
Most mutations will not be beneficial and will stop the spike protein from working or have no effect on its function. But some can cause changes that give the new version of the virus a selective advantage by making it more transmittable or infectious. One way this could occur is through a mutation in a part of the spike protein that prevents protective antibodies from binding to it. Another way would be to make the spikes more “sticky” for our cells.
This is why new mutations that alter the way the spike works are of particular concern: They may affect how we control the spread of SARS-CoV-2. Newer variants found in the UK and elsewhere have mutations in spikes and in parts of the protein involved in entering cells. Experiments will need to be performed in the laboratory to determine if, and how, these mutations significantly shift the peak, and if our current control measures are still effective.