The emergence of a new variant of the coronavirus has sparked renewed interest in the part of the virus known as the spike protein.
The new variant has several peculiar changes in the spike protein compared to other closely related variants – which is one reason why it is more concerning than other harmless changes in the virus that we have seen before. The new mutations can alter the biochemistry of the spike and can affect how transmissible the virus is.
The spike protein is also the basis of current COVID-19 vaccines, which try to generate an immune response against it. But what exactly is the spike protein and why is it so important?
Cell invaders
In the world of parasites, many bacterial or fungal pathogens can survive on their own without a host cell being able to infect. But viruses cannot. Instead, they have to get into 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 ward off such invaders. One of the most important defenses of cellular life against invaders is the outer layer, which is made up of a fat layer that contains all the enzymes, proteins and DNA of a cell.
Due to the biochemical nature of fats, the outer surface is highly negatively charged and repellent. Viruses have to cross this barrier to access the cell.
How SARS-CoV-2 gets into cells and reproduces. (Pislar et al., PLoS Pathog, 2020, CC BY)
Like cellular life, coronaviruses themselves are surrounded by a fat membrane known as an envelope. To gain access to the inside of the cell, enveloped viruses use proteins (or glycoproteins, as they are often covered with slippery sugar molecules) to fuse their own membrane with that of cells and take over the cell.
The peak protein of coronaviruses is one such viral glycoprotein. Ebola viruses have one, the influenza virus has two, and the herpes simplex virus has five.
The architecture of the peak
The spike protein is composed of a linear chain of 1,273 amino acids, neatly folded into a structure studded with up to 23 sugar molecules. Spike proteins like to stick together and three separate spike molecules bind together to form a functional “trimer” unit.
The peak can be divided into different functional units, known as domains, that perform different biochemical functions of the protein, such as binding to the target cell, fusing with the membrane, and leaving the peak on the viral envelope.
The SARS-CoV-2 spike protein is attached to the roughly spherical viral particle, embedded in the envelope, and projects into space, ready to cling to unsuspecting cells. It is estimated to be about 26 peak trimers per virus.
The spike protein is made up of different sections that perform different functions. (Rohan Bir Singh, CC BY)
One of these functional units binds to a protein on the surface of our cells called ACE2, which triggers the uptake of the virus particle and eventually membrane fusion. The peak is also involved in other processes such as assembly, structural stability, and immune evasion.
Vaccine vs Spike Protein
Given how crucial the spike protein is to the virus, many antiviral vaccines or drugs target viral glycoproteins.
For SARS-CoV-2, the vaccines produced by Pfizer / BioNTech and Moderna instruct our immune system to make our own version of the spike protein, which is done shortly after immunization. The production of the spike in our cells then starts the process of producing protective antibodies and T cells.
One of the most concerning features of the SARS-CoV-2 spike protein is how it moves or changes over time during the evolution of the virus. Encoded in the viral genome, the protein can mutate and change its biochemical properties as the virus evolves.
Most mutations will not be beneficial and 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 transmissible or infectious.
One way this can happen is through a mutation on part of the spike protein that prevents protective antibodies from binding to it. Another way would be to make the dots “stickier” to our cells.
This is why new mutations that change the way peak functions are of particular interest – they may affect how we control the spread of SARS-CoV-2. The new variants found in the UK and elsewhere have mutations in the spike and in parts of the protein involved in entering your cells.
Experiments will need to be performed in the laboratory to determine whether – and how – these mutations significantly alter the peak and whether our current controls remain effective.
Connor Bamford, Research Fellow, Virology, Queen’s University Belfast.
This article has been republished from The Conversation under a Creative Commons license. Read the original article.