The EARS-CoV-2 virus mutates rapidly. This is worrying because these more transmissible variants of SARS-CoV-2 are now found in the US, UK and South Africa and other countries, and many people are wondering if the current vaccines will protect the recipients against the virus. Furthermore, many people are asking if we will be able to predict future variants of SARS-CoV-2, which will definitely emerge.
In my laboratory I study the molecular structure of RNA viruses – as the cause COVID-19 – and how they repeat and multiply in the host. As the virus infects more people and spreads the pandemic, SARS-CoV-2 continues to evolve. This evolutionary process is constant and it enables the virus to sample its environment and make changes that make it grow more efficiently. It is therefore important to monitor viruses for such new mutations that may make them more lethal, more transmissible, or both.
RNA viruses develop rapidly
The genetic material of all viruses is encoded in one of the two DNA or RNA; an interesting feature of RNA viruses is that they change much faster than DNA viruses. Every time they make a copy of their genes, they make one or a few mistakes. It is expected to occur many times in the body of an individual infected with COVID-19.
One might think that an error in your genetic information is bad – after all, it is the basis for genetic diseases in humans. For an RNA virus, a single change in its genome can ‘kill’ it. It’s not bad if you make thousands of copies in an infected human cell, and some of them are no longer useful.
However, some genomes may pick up a change that is beneficial for the survival of the virus: Perhaps the change allows the virus to evade an antibody – a protein that the immune system produces to catch viruses – or an antiviral agent . Another beneficial change may allow the virus to infect a different type of cell or even a different animal species. This is probably the path that SARS-CoV-2 could move from bats to humans.
Any change that gives the descendants of the virus a competitive growth advantage is favored – “selected” – and the original parent virus begins to outgrow this. SARS-CoV-2 now demonstrates this feature with new variants that enhance growth characteristics. Understanding the nature of these changes in the genome will guide scientists to develop countermeasures. This is the classic cat-and-mouse scenario.
In an infected patient, there are hundreds of millions of individual virus particles. If you were to detect one virus in this patient at the same time, you would find a variety of mutations or variants in the mixture. It’s the question of which one has a growth advantage – that is, which can develop because it is better than the original virus. These are the ones who are going to be successful during the pandemic.
Is it particularly worrying about the mutations detected?
Any single variant or change in the virus is probably not that problematic. A single change in the vein protein – which is the region of the virus that attaches to human cells – is probably not a major threat as the medical community rolls out the vaccines.
The current vaccines cause the immune system to produce antibodies that recognize and target the ear protein on the virus, which is essential for the penetration of human cells. Scientists have observed the accumulation of multiple changes in the vein protein in the South African variant.
With these changes, for example, SARS-CoV-2 can attach more strongly to the ACE2 receptor and invade human cells more effectively, according to preliminary unpublished studies. These changes can enable the virus to infect cells more easily and improve their transmissibility. With multiple changes in the vein protein, the vaccines can no longer produce a strong immune response against these new variant viruses. This is a double whammy: a less effective vaccine and a more robust virus.
At the moment, the public does not have to worry about the current vaccines. The leading vaccine manufacturers are monitoring how well their vaccines control these new variants, and are ready to adapt the vaccine design to ensure that they are protected against these emerging variants. Moderna, for example, has stated that it will adjust the second or booster injection to further adjust the sequence of the South African variant. We’ll just have to wait and see, as more people get vaccinated, or the transmission rate drops.
Why does the transmission key drop?
A decrease in transmission rates means fewer infections. Less virus replication leads to fewer opportunities for the virus to develop in humans. With less chance of mutating, the evolution of the virus slows down and there is a lower risk for new variants.
The medical community must make a great effort and have as many people as possible vaccinated and protected. If not, the virus will continue to grow in large numbers of people and produce new variants.
How the new variants differ
The British variant, known as B.1.1.7., Appears to bind more strongly to the protein receptor called ACE2, which is on the surface of human cells.
I do not think we have seen clear evidence that these viruses are more pathogenic, which is more deadly. But they can be transferred faster or more efficiently. This means that more people will be infected, which means that more people will be admitted to hospital.
The South African variant, known as 501.V2, has multiple mutations in the gene that encodes the vein protein. These mutations help the virus evade an antibody response.
Antibodies have excellent precision for their target, and if the target changes shape slightly, as with this variant – which virologists call an escape mutant – the antibody can no longer bind tightly because it loses its protective ability.
Why should we monitor for mutations?
We want to make sure that all the viruses are detected in the diagnostic tests. If there are mutations in the genetic material of the virus, an antibody or PCR test may not detect it as effectively or at all.
To make sure the vaccine is going to be effective, researchers need to know if the virus is developing and the antibodies caused by the vaccine are escaping.
Another reason why monitoring new variants is important is that people who are infected can become infected again if the virus has mutated and their immune system cannot recognize it and turn it off.
The best way to look for emerging variants in the population is to do random sequencing of the SARS-CoV-2 viruses from patient samples across different genetic backgrounds and geographical locations.
The more sequence data researchers collect, the better vaccine developers can respond in advance to major changes in the virus population. Many research centers across the US and the world are increasing their sequencing capabilities to accomplish this.
Written by Richard Kuhn, Professor of Biological Sciences, Purdue University.
Originally published on The Conversation.