Since the beginning of the Covid-19 pandemic, it has been frequent to hear comments about the fear that SARS-CoV-2 would mutate into a more aggressive form. In the minds of many people, the virus was visualized as an entity capable of making decisions to ensure its permanence among us.
United Kingdom warns that the new variant of the coronavirus could be up to 30% more lethal
The reality is that viruses decide nothing. Simply, when they infect a cell, almost automatically, they begin to multiply, something that includes copying their genetic information. During the copying process it is common for errors to appear, which, although many times have no effect, sometimes produce changes in some of the amino acids that make up the proteins of the virus. As a consequence, 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
If viruses continually mutate, why is it now that there seem to be more variants of SARS-CoV-2? Because we are putting obstacles to its transmission.
Things were very different at the beginning of the pandemic. We were all susceptible to SARS-CoV-2, there was a great shortage of protective equipment to prevent infections and, furthermore, we were unaware of the best measures to prevent them. The result is that the virus practically had a clear path to infect us, and variants that were slightly more contagious had little advantage over the rest.
After a year of pandemic, the situation has changed. Many people have already passed the infection and have antibodies against the virus. We have access to masks and we have learned that the virus is transmitted by aerosols, which allows us to avoid contagion with good ventilation. Finally, a vaccination process has begun which in some countries 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, being able to become the majority.
More contagion does not mean more lethality
There are several ways in which a virus can enhance its transmission. One of them is to increase its ability to interact with the cell receptor, the molecule that allows it to enter the cell. Another, in populations with an abundance of individuals who have already passed the infection, is avoiding being recognized by the antibodies. The good news is that greater contagion capacity is not usually associated with increases in fatality. The virus is not interested, because if an infected individual dies early or develops very severe symptoms, they will be less likely to transmit it.
The variants of SARS-CoV-2 that currently cause the most concern, due to the rapidity with which they are spreading, are the british, the South African and the Brazilian, named for the place where they were first detected. According the most widely accepted nomenclature for classifying 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 coincident. Of these, the most worrying are those that are located in protein S or spicule, which is the one that interacts with the cellular receptor and towards which a large part of the immune response is directed. We still don’t know much about these mutations, but we are beginning to have some clues. However, it must be borne in mind that the possible advantages of a viral variant are not usually 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 spike with a tyrosine, is common to all three variants and produces a change in structure in this protein that increases its ability to bind to the cell receptor. It’s like tuning a key to better fit your lock.
The E484K mutation, present in the Brazilian and South African variants, has also been identified in the spicule. Everything indicates that, in addition to favoring receptor binding, it could make the virus worse neutralized by antibodies, thus increasing reinfections or decreasing the effectiveness 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 elimination of amino acids at positions 69 and 70 of the spike. The mutation, which was also detected in viruses isolated from massive infections that took place on several mink farms a few months ago in Holland and Denmark, shows how the spread of the virus in species other than humans it can favor the appearance of new variants that are more dangerous for us. Specifically, this mutation appears to act in synergy with the N501Y, described above, further increasing the affinity for the receptor.
Is it the deadliest British variant?
In recent days, doubts have been raised about whether the British variant is more lethal in elderly people. The reality is that any more transmissible variant will increase the death toll, 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 frequency of reinfections, as has been commented in the case of the South African and Brazilian variants. The truth is that most of the studies on the effect of antibodies on these viruses have been carried out in in vitro tests, which do not take into account the complex immune response that is generated in an organism.
If the lower effectiveness of vaccines against these variants were confirmed, it would not be a debacle. It would simply imply that vaccines would have to be periodically updated based on the strains in circulation at the time. This is common with the flu virus, which could even be much more manageable with the newer RNA vaccines. Once again we are witnessing how scientific research is the best ally for our survival.