Why is the mutation discovered in the UK so concerned?

A recurring phrase in the course of this Sars-CoV-2 pandemic is that this new coronavirus, like all viruses that contain RNA as genetic material, are viruses that mutate and that this one in particular, mutates less than the influenza virus.

So if mutations in viruses are to be expected, why is the new variant detected this weekend in the UK so striking? The key again is in the Spike (S) or Spike Protein.

As reported by UK authorities, the new variant called VUI 202012/01 (Variant in research, year 2020, month 12, variant 01) has multiple spike protein mutations (deletion 69-70, deletion 145, N501Y, A570D, D614G, P681H, T716I, S982A, D1118H). Further, it has other mutations elsewhere in the virus genome.

But beyond the number of mutations, researchers warn that viruses naturally mutate And most of the time, these types of mutations are simply regional neutral markers useful for contact tracing and thus knowing where it comes from. “The mutations observed have rarely affected viral fitness and they almost never affect the clinical outcome, but the detailed effects of these mutations have not yet been fully determined, “they warn.

Each time a virus enters a cell to infect it, it replicates in it and mistakenly transfers different information, which is what determines new combinations or mutations.

Vivian Luchsinger, virologist and researcher of the Institute of Biomedical Sciences (ICBM) since Faculty of Medicine of the University of Chile, points out that viruses with RNA when entering the cell and reproducing in it, use enzymes to produce new RNA particles in the children of these viruses, but this enzyme is wrong and instead of putting one nucleotide, it puts another. “Most of the changes are not important but these changes can occur in any protein of the virus. If there are changes in the proteins that are related to the antibodies, it may be that the protein it produces is not detected by the antibodies, ”he explains.

In this specific case, says Luchsinger, “it is known to have 17 changes or mutations and the most important is one that it has in the Spike protein, which is the protein that attaches itself to the cell it infects. The appearance of the new variant of the virus coincides in time with an area in which an increase in cases has been seen. According to the surveillance that has been carried out, in places where there has been an increase, when doing genetic sequencing, this virus has been seen. It is a temporary association, but it must be studied to see if they have ruled out any change in the behavior of the virus. “

Nicolás Muena, a researcher at the Science & Life Foundation, explains that for now it is a variant of the same SARS-CoV-2 virus, just as many have been detected since its appearance. “Until there is more evidence that the mutation changes the relationship with antibodies, or that it is capable of evading the immune system or that there is variation in the immunological or biological characteristics of the virus, they keep talking about variant or lineage. Not all variants are transformed into a new virus strain, for that there must be a change in behavior ”, he says.

For now, suspicions suggest that the new variant would have a higher transmissibility, but it is not conclusive yet as laboratory studies are lacking.

However, according to Muena there are several situations that attract attention. The first is the great speed with which this variant has gained space. When it was discovered in September, its circulation reached 25% – that is, of all the samples that were sequenced, 25% corresponded to this variant – but now it reaches 60%.

Another striking aspect is the number of mutations that were concentrated in the Spike protein. “The hypothesis that is handled is that it may have arisen from a person who became chronically ill from Covid-19. Some immunocompromised person in which the virus kept replicating for a constant period without the immune system being able to eliminate it ”, indicates the researcher.

In this same protein, it maintains a mutation in a place called N501Y, which is right in the area where Spike binds to cells, which in theory could improve this ability. Further, has a deletion, that is, two amino acids were deleted (69-70), a change that has previously been described as an evasion of the immune system (some antibodies) and that in theory could increase the force with which it binds to the cell.

Mutations N501Y, D614G, and deletions 69-70 are not new, but they have never been seen together before, in the same variant, says Muena.

Alexis Kalergis, academic at the Catholic University and director of the Millennium Institute of Immunology and Immunotherapy (IMII), points out that according to the report delivered by the European Center for Disease Control (ECDC), it would be a new variant that presents several genetic changes and suggests that it would have the ability to be more communicable, but would not cause more serious disease. “However, it is too early to draw definitive conclusions, since it requires a series of tests that will take time.”

“Mutations in the genomes of viruses are to be expected, but you cannot predict where in the genome or when they will occur, and neither can their biological or immunological implications,” says Kalergis.

For Andrea Silva, Biologist and Doctor of Science and Executive Director of Austral Omics, unit of Innovation in Biotechnology of the Faculty of Sciences Austral University (UACh), for it to be a new strain it is essential that the virus behaves differently in humans, that it is more contagious, more virulent, but for now all of that is speculative. “It is believed that it is transmitted faster, but the mechanism by which this occurs is not yet clear.”

Another aspect that should be considered according to Silva is the United Kingdom is one of the countries that performs the most genetic sequencing, so its detection does not imply that the mutation has occurred there. It may be that the variant has been around for a long time and has only now been detected.

Given the changes that the virus is having, will the vaccines that are being developed work? According to Kalergis, who is also general director of the clinical trial of the Sinovac and Biotech vaccine, there is still a need to study.

“There is still no evidence that this variation can evade the immune response generated by vaccines, but nevertheless it must be studied. For example, evaluate the neutralizing capacity of this new variant of the virus with the antibodies generated by the vaccines. However, it is important to indicate that the vaccines have shown high efficacy against the SARS-CoV-2 virus, and the immune system does not recognize a single place on the protein to mount an immune response, but is capable of recognizing several points inside a protein ””.

Even so, he warns that the evolution of the virus and its implication in people who were vaccinated should be closely followed, as well as the results of neutralization that can be performed with sera from people immunized with the vaccines currently in use.

The variants identified have been mainly in the protein Spike. The information that is not yet known is whether these mutations interfere with the neutralizing capacity of antibodies or with the activation of T lymphocytes. The truth is that vaccines based only on Spike could be more vulnerable to the evasion of immunity by of the virus, because these vaccines only induce immunity against Spike. Inactivated virus-based vaccines contain all the other virus proteins in addition to Spike, so the immunity they generate may be less vulnerable to evasion by variants of the virus with changes in Spike. However, it is necessary to do the corresponding studies ”, warns the IMII director.

Muena believes that many mutations are necessary for vaccines that work with the Spike protein to lose effectiveness and insists that “the changes that have occurred so far are not enough to evade the immune response generated by the vaccines” and even, if they occurred, ” it would be easy to include new genetic information in vaccines because that information can be adapted to vaccine technology ”.

The minister of Science Technology, Knowledge and Innovation, Andres Couve, notes that the UK mutation affects the spread of the virus and makes it more rapid, but it is not yet known whether it is more virulent. To date, it says, the Sars-CoV-2 virus registers more than 12 thousand mutations.

“To understand this phenomenon and work on genomic surveillance”, tomorrow the Ministry of Science, the Institute of Public Health of Chile (ISP), the Consortium of Universities and the Department of Epidemiology of the Ministry of Health will meet urgently to “face as a whole this new edge of the pandemic ”, Couve said.

Consulted the Health Minister, Enrique Paris, He said that according to the information provided by the World Health Organization (WHO), the variant would be more contagious, which forces to reinforce the measures. For this reason, he announced that a work team was created with the Ministry of Sciences to analyze the sequencing of the virus in Chile and thus detect the variable by PCR. “We know that ISP can do genomic monitoring for sequencing, but we will request the collaboration of universities throughout Chile.”