The emergence of a new variant of coronavirus has aroused renewed interest in the part of the virus known as the spike protein.
The new variant has some special changes in the spike protein compared to other closely related variants – and this is one of the reasons why it is more worrying than other harmless changes in the virus that we have seen before. New mutations can change the biochemistry of the tip and could affect how transmissible the virus is.
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?
Cell invaders
In the world of parasites, many bacterial or fungal pathogens can survive on their own without a host cell becoming infected. But viruses can’t. Instead, they must penetrate inside the cells to replicate, where they use the cell’s own biochemical machines to build new virus particles and spread to other cells or individuals.
Our cells have evolved to avoid these intrusions. One of the major defenses of cell life against invaders is the outer covering, which is composed 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 strongly negatively charged and repels. Viruses must cross this barrier to gain access to the cell.
How SARS-CoV-2 enters cells and reproduces. (Pislar et al., PLoS Pathog, 2020, CC BY)
Like cell life, coronaviruses are surrounded by a fatty membrane known as the sheath. To enter the cell, the enveloped viruses use proteins (or glycoproteins because they are frequently covered by slippery sugar molecules) to fuse their own membrane with that of the cells and take over the cell.
Coronavirus spike protein is one such viral glycoprotein. Ebola viruses have one, the flu virus has two, and the herpes simplex virus has five.
The architecture of the top
The spike protein is composed of a linear chain of 1,273 amino acids, beautifully folded into a structure that is studded with up to 23 sugar molecules. Spike proteins like to stick together and three separate spike molecules bind to each other to form a “trimeric” functional unit.
The spike can be divided into distinct 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 allowing the tip to remain on the viral envelope.
The spike protein of SARS-CoV-2 is blocked on the approximately spherical viral particle, embedded in the envelope and projected into space, ready to cling to unsuspected cells. It is estimated that there are approximately 26 peaks per virus.
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, triggering the absorption of the virus particle and eventually membrane fusion. Peak is also involved in other processes, such as assembly, structural stability, and immune evasion.
Vaccine vs. protein spike
Given the importance of spike protein for the virus, many antiviral vaccines or drugs are targeted to viral glycoproteins.
For SARS-CoV-2, the vaccines produced by Pfizer / BioNTech and Moderna provide instructions to our immune system to create our own version of the spike protein, which occurs shortly after immunization. The production of the peak inside our cells then begins the process of producing protective antibodies and T cells.
One of the most worrying features of the SARS-CoV-2 spike protein is the way it moves or changes over time during the evolution of the virus. Coded in the viral genome, the protein can move and change its biochemical properties as the virus evolves.
Most mutations will not be beneficial and will either stop the functioning of the spike protein or have no effect on its function. But some can cause changes that give the new version of the virus a selective advantage, making it more transmissible or infectious.
One way this could occur is through a mutation on one side of the spike protein that prevents the binding of protective antibodies to it. Another way would be to make the tips “more sticky” for our cells.
This is why new mutations that change the way peak functions are particularly worrying – can affect the way we control the spread of SARS-CoV-2. New variants found in the UK and elsewhere show mutations in the tips and parts of the proteins 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 control measures remain effective.
Connor Bamford, researcher, Virology, Queen’s University Belfast.
This article is republished from Conversation under a Creative Commons license. Read the original article.