By Richard Kuhn
The SARS-CoV-2 virus is rapidly rolling out. That’s a concern because these more transmissible variants of SARS-CoV-2 are now present in the US, UK and South Africa and other countries, and many people are wondering whether the current vaccines will protect recipients against the virus. Moreover, many question whether we will be able to keep ahead of future variants of SARS-CoV-2, which will certainly arise.
In my lab I’m studying the molecular structure of RNA viruses – like the one that causes COVID-19 – and how they replicate and multiply in the host. As the virus infects more people and the pandemic spreads, SARS-CoV-2 continues to evolve. This evolution process is constant and allows the virus to taste its environment and choose changes that make it grow more efficiently. Therefore, it is important to monitor viruses for such new mutations that may make them more deadly, more transmissible or both.
RNA viruses are evolving rapidly
The genetic material of each virus is encoded in either DNA or RNA; one interesting feature of RNA viruses is that they change much faster than DNA viruses. Every time they copy their genes they make one or a few mistakes. This is expected to happen many times in the body of a person infected with COVID-19.
Someone may think that making a mistake in your genetic information is bad – after all, that is the basis for genetic diseases in humans. For an RNA virus, one change in its genome can make it “dead.” It’s not too bad if you’re making thousands of copies inside an infected human cell and a few are no longer useful.
However, some genomes may indicate a change that is beneficial for the survival of the virus: The switch may allow the virus to avoid an antibody – a protein the immune system produces to trap viruses – or an antiviral drug. Another beneficial change may be allowing the virus to infect a different cell type or even a different species of animal. This is probably the path that allowed SARS-CoV-2 to move from bats to humans.
Any change that gives the virus descendants a competitive growth advantage will be favored – “selected” – and begin to grow too large for the original parent virus. SARS-CoV-2 is now showcasing this feature with new variants coming up that have improved growth properties. Understanding the nature of these changes in the genome will guide scientists in developing countermeasures. This is the classic cat and mouse scenario.
In an infected patient there are hundreds of millions of individual virus particles. If you went in and selected one virus at a time in this patient, you would find a range of mutations or variations in the mix. It is a question of which ones have a growth advantage – that is, which ones can evolve because they are better than the original virus. Those are the ones that are going to become successful during the pandemic.
Of the mutations found, is one of particular concern?
Any single variation or change in the virus is probably not that problematic. One change in the spike protein – the region of the virus that binds to human cells – is unlikely to pose a major threat as the medical community introduces the vaccines.
Current vaccines induce the immune system to produce antibodies that recognize and target the spike protein on the virus, which is essential for invading human cells. Scientists have observed accumulation of multiple changes in the spike protein in variation in South Africa.
These changes allow SARS-CoV-2, for example, to attach more tightly to the ACE2 receptor and enter human cells more efficiently, according to unpublished preliminary studies. Those changes could enable the virus to more easily infect cells and improve its transferability. With several changes in the spike protein, the vaccines may no longer produce a strong immune response against these new variant viruses. That’s a double whammy: a less effective vaccine and a more robust virus.
At present, the public does not need to worry about current vaccines. Leading vaccine manufacturers are monitoring how well their vaccines are managing these new variants and are ready to change the design of the vaccine to ensure they protect against these emerging variants. Moderna, for example, has indicated that it will modify the second injection or booster injection to more closely match the South African variation sequence. We will have to wait to see, as more people receive vaccinations, whether transmission rates fall.
Why is reducing transmission key?
Reduced transmission rates mean fewer infections. Reduced virus replication leads to fewer opportunities for the virus to evolve in humans. With less chance of mutation, the evolution of the virus slows down and there is a lower risk of new variants.
The medical community needs to push big and get as many people vaccinated and therefore protected as possible. If not, the virus will continue to grow in large numbers of people and produce new variants.
How are the new variants different
The UK variant, known as B.1.1.7., Appears to bind more tightly to the protein receptor called ACE2, which is on the surface of human cells.
I don’t think we’ve seen clear evidence that these viruses are more pathogenic, meaning more deadly. But they can be transmitted faster or more efficiently. That means more people will become infected, which means more people who will be in hospital.
The South African variant, known as 501.V2, has multiple mutations in the gene encoding the spike protein. These mutations help the virus avoid an antibody response.
Antibodies have fine 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, thus that he lost his power of defense.
Why do we need to monitor mutations?
We want to make sure that the diagnostic tests detect all the viruses. If there are mutations in the genetic material of the virus, an antibody or PCR test may not be able to detect it as efficiently or at all.
To ensure the vaccine is going to be effective, researchers need to know whether the virus is evolving and escaping the antibodies induced through the vaccine.
Another reason that monitoring for new variants is important is that infected people may become infected again if the virus has rolled around and their immune system cannot recognize and shut it down.
The best way to look for emerging population variations is to randomly sequence SARS-CoV-2 viruses from patient samples across diverse genetic backgrounds and geographic locations.
The more sequencing data that researchers collect, the better vaccine developers will be able to respond before major changes in the virus population. Many research centers around the US and the world are increasing their sequencing capabilities to achieve this.