The science you need to understand

The SARS-CoV-2 virus mutates rapidly. This is a problem because these more transmissible variants of SARS-CoV-2 are now found in the US, UK, South Africa and other countries, and many people are wondering if current vaccines protect recipients of the virus. In addition, many are wondering if we will be able to stay ahead of future variants of SARS-CoV-2, which will certainly happen.

In my lab, I study 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 evolutionary process is constant and allows the virus to sample its environment and select the changes that make it grow more efficiently. Thus, it is important to monitor viruses for such new mutations which could make them more deadly, more transmissible, or both.

RNA viruses evolve rapidly

The genetic material of all viruses is encoded in 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. This is expected to happen multiple times in the body of an individual infected with COVID-19.

You might think that getting your genetic information wrong is bad – after all, it is the basis of genetic diseases in humans. For an RNA virus, a single modification of its genome can make it “dead”. It’s not too bad if inside an infected human cell you make thousands of copies and a few are no longer useful.

However, some genomes may take a change that is beneficial for the survival of the virus: perhaps the change allows the virus to escape an antibody – a protein that the immune system makes to catch viruses – or an antiviral drug. . Another beneficial change can allow the virus to infect a different type of cell or even a different animal species. This is probably the route that allowed SARS-CoV-2 to pass from bats to humans.

Any change that gives offspring of the virus a competitive growth advantage will be favored – “selected” – and begin to overtake the original parent virus. SARS-CoV-2 demonstrates this characteristic now with new variants that have improved growth properties. Understanding the nature of these changes in the genome will provide scientists with advice to develop countermeasures. This is the classic cat and mouse scenario.

In an infected patient, there are hundreds of millions of individual viral particles. If you were to go in and pick one virus at a time in this patient, you would find a range of mutations or variants in the mix. It’s a matter of which ones have a growth advantage, i.e. which ones can evolve because they are better than the original virus. These are the ones who will be successful during the pandemic.

Among the mutations that have been detected, is this one of the most worrying?

Any variation or modification of the virus is probably not that problematic. A single change in the spike protein – which is the region of the virus that attaches to human cells – is unlikely to pose a big threat as the medical community rolls out 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 observed the accumulation of multiple changes in the spike protein in the South African variant.

These changes allow SARS-CoV-2, for example, to bind more tightly to the ACE2 receptor and enter human cells more efficiently, according to preliminary unpublished studies. These changes could make it easier for the virus to infect cells and improve its transmissibility. With multiple changes in the spike protein, vaccines may no longer produce a strong immune response against these novel variant viruses. It’s a double whammy: a less effective vaccine and a more robust virus.

Today, the public does not need to be concerned with current vaccines. Major vaccine manufacturers are monitoring how well their vaccines control these new variants and are ready to fine-tune the vaccine design to ensure they protect against these emerging variants. Moderna, for example, said she would adjust the second injection or booster injection to more closely match the sequence of the South African variant. We’ll just have to wait and see, as more people get vaccinated, whether transmission rates go down.

Why lower the transmission key?

Lower transmission rates mean fewer infections. Less viral replication leads to fewer opportunities for the virus to evolve in humans. With less chance of mutating, the evolution of the virus slows down and the risk of new variants is lower.

The medical community must make a great effort to vaccinate as many people as possible and thus protect them. Otherwise, the virus will continue to grow in a large number of people and produce new variants.

How the new variants are different

The British variant, known as B.1.1.7., Appears to bind more tightly to the protein receptor called ACE2, which is found on the surface of human cells.

I don’t think we’ve seen clear evidence that these viruses are more pathogenic, which means more deadly. But they can be transmitted faster or more efficiently. This means that more people will be infected, which translates to more people being hospitalized.

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The South African variant, known as 501.V2, has multiple mutations in the gene that encodes the spike protein. These mutations help the virus escape an antibody response.

Antibodies have exquisite 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, as it loses its power to protection.

Why do we need to watch for mutations?

We want to make sure that the diagnostic tests detect all 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 effectively or at all.

To be sure the vaccine will work, researchers need to know if the virus is changing and escaping the antibodies that were triggered by the vaccine.

Another reason why monitoring for new variants is important is that people who have been infected could be infected again if the virus has mutated and their immune system cannot recognize and stop it.

The best way to look for emerging variants in the population is to randomly sequencing SARS-CoV-2 viruses from patient samples from various genetic backgrounds and geographic locations.

The more sequencing data researchers collect, the better vaccine developers will be able to respond to major changes in the viral population. Many research centers in the United States and around the world are strengthening their sequencing capabilities to achieve this.