Viruses mutate all the time, but why is it that more SARS-CoV-2 strains seem to be appearing now? When they infect a cell, they simply begin to multiply almost automatically, including copying their genetic information.
Since the beginning of the Covid-19 pandemic, it has been common to hear comments about the fear that SARS-CoV-2 would mutate into a more aggressive form. In many people’s minds, the virus was envisioned as an entity capable of making decisions to ensure its permanence among us.
The reality is that viruses do not make decisions. When they infect a cell, they simply begin to multiply almost automatically, including copying their genetic information. During the copying process, errors often occur, which, although they often have no effect, sometimes lead to changes in some of the amino acids that make up the virus’ proteins. As a result, the three-dimensional structure of these macromolecules can be altered, and with it the properties of the virus.
More SARS-CoV-2 variants than ever before
If viruses mutate continuously, why is it that there seem to be more variants of SARS-CoV-2 now? Because we’re putting obstacles in the way of its transmission.
Things were very different at the beginning of the pandemic. We were all susceptible to SARS-CoV-2, there was a severe shortage of protective equipment to prevent infection, and we didn’t know the best measures to prevent it. As a result, the virus had a virtually free rein to infect us, and the variants that were slightly more contagious had little advantage over the rest.
A year into the pandemic, the situation has changed. Many people are now infected and have antibodies to the virus. We have access to masks, and we have learned that the virus is transmitted by aerosols, which makes it possible to avoid infection with good ventilation. Finally, a vaccination process has started, and in some countries, it has already reached a large part of the population.
In short, we are making it increasingly difficult for the virus. And a direct consequence is that, under pressure, the most transmissible variants have an advantage over the rest and can become the majority.
More transmission does not mean more lethality
There are several ways in which a virus can improve its transmission. One is to increase its ability to interact with the cellular receptor, the molecule that allows it to enter the cell. Another, in populations with an abundance of individuals who have already been infected, is to avoid being recognized by antibodies. The good news is that increased infectiousness is not usually associated with increased lethality. The virus does not care because if an infected individual dies early or develops very severe symptoms, he or she is less likely to transmit it.
The variants of SARS-CoV-2 that are currently causing the most concern, due to the speed at which they are spreading, are the British, South African, and Brazilian variants, named after the place where they were first detected. According to the most widely accepted nomenclature for the classification of virus lines, these variants correspond to B.1.1.7 (British), B.1.351 (South African), and P.1 (Brazilian).
Each of these lines contains a particular set of mutations, some of which are coincidental. Of these, the most worrying are those in the S or spicule protein, which interacts with the cellular receptor and towards which much of the immune response is directed. We still do not know much about these mutations, but we are beginning to get some clues. However, it should be noted that the potential advantages of a viral variant are often not due to a single mutation but to a combination of several.
What mutations do the new SARS-CoV-2 variants contain?
The N501Y mutation, which replaces the amino acid asparagine at position 501 of the spicule with a tyrosine, is common to all three variants and causes a change in the structure of the protein that increases its ability to bind to the cellular receptor. It is as if we were tuning a key to make it fit better in its lock.
The E484K mutation, present in the Brazilian and South African variants, has also been identified in the spicule. It suggests that, in addition to favoring receptor binding, it could make the virus less well neutralized by antibodies, thus increasing reinfection or decreasing the efficacy of vaccines.
The finding of these mutations in viral genomes isolated in different parts of the world, and belonging to different evolutionary lines, is another indicator of their possible advantage over viruses that do not contain them.
Another interesting mutation is the deletion of amino acids at positions 69 and 70 of the spicule. The mutation, which was also detected in viruses isolated from mass infections that took place in several mink farms a few months ago in the Netherlands and Denmark, demonstrates how the spread of the virus in species other than humans can favor the emergence of new variants that are more dangerous to us. In particular, this mutation appears to act in synergy with the previously described N501Y, further increasing the affinity for the receptor.
Is the British variant more deadly?
In recent days, questions have been raised about whether the British variant is more deadly in older people. The reality is that any more transmissible variant will increase the number of deaths, not only because of the greater number of infections but also because of the greater difficulties in treating the sick.
There is also great concern about whether the circulation of these variants will affect the efficacy of vaccines or the frequency of reinfection, as has been discussed in the case of the South African and Brazilian variants. Indeed, most studies on the effect of antibodies on these viruses have been conducted in vitro assays, which do not take into account the complex immune response generated in an organism.
If the reduced effectiveness of vaccines against these variants were confirmed, it would not be a debacle. It would simply mean that vaccines would have to be periodically updated according to the strains that are in circulation at the time. This is common with the influenza virus and might even be much more manageable with the new RNA vaccines. Once again, we see how scientific research is the best ally for our survival.