[ad_1]
Notice to readers: EL PAÍS keeps open essential information about the coronavirus during the crisis. If you want to support our journalism, Click here for subscribe.
Every time a virus enters a new host, nature speeds up evolution. The pathogen has to adapt to the new animal, learn to unlock its cells, enter them, and use its mechanism to make tens of thousands of copies of itself.
In the new host, the rate of evolution of the virus accelerates, and it is likely to change to be more efficient. Here’s what may have happened to the coronavirus detected in Denmark: It first jumped from humans to minks, adapted to infect these animals, undergoing four changes, or mutations, in its genetic sequence along the way, and then began to jump again. for humans, probably farm workers. This launched a new variant of the coronavirus with four new mutations that target the most important part of the pathogen: the S protein that is essential for infecting SARS-CoV-2 and that is the target of many of the vaccines that are in development. . . Although the possibility that these changes will reduce the effectiveness of vaccines is remote, Denmark has made the decision to annihilate all its minks – some 17 million – and confine some 280,000 people who live in areas where the new variant already circulates. of the virus. among humans.
More information
Much of this decision is based on a laboratory experiment of which there are few details. Scientists at the Danish Serological Institute have tested whether antibodies generated by people who have passed the conventional coronavirus could also fight the new mutant variant of the mink. The results show that human antibodies do not neutralize this new variant as much as conventional ones, although there are no details of how much or why it occurs. This virus is known as variant 5, since four other versions of the coronavirus were detected, which also circulated among minks. It is already known that the former is neutralizable with human antibodies. The other three are under study and it will still take “weeks” to obtain the results, according to the Sorological Institute.
Denmark was one of the European countries that so far best contained the spread of the coronavirus by taking drastic containment and testing measures in the first months of the pandemic. The authorities have known since the summer that the coronavirus had jumped to the mink and was circulating in the farms of the country, which is the world’s largest producer of fur from these animals. At the moment, 214 people have been infected with any of the five variants of the mink virus. Two hundred of them are in the area of the outbreak, in North Jutland, which means that 40% of all infected people detected in this area are carriers of the mink virus. Twelve of those infected are carriers of variant 5. Eleven are from northern Jutland, but one was identified in Zealand, another island in the country, indicating that the variant came out of the original area of the outbreak. This is the variant of most concern now because it accumulates four mutations in protein S.
A mutation is a misprint in the virus’s instruction book – its genome – that contains a sequence of 30,000 genetic letters whose order is fundamental. Every time the virus makes a copy of itself, and is capable of making tens of thousands by infecting a single cell, copy errors can occur in its genome. The vast majority of these errors have no effect, but some of them may give the virus a greater ability to infect or spread, especially if they are in protein S. At the moment, there is no data that indicates that any of the four mutations identified in the Danish virus alter the contagion power of the coronavirus or its ability to spread. The Danish Government guarantees that the symptoms and virulence of this variant are not different from those of previously known variants.
The four mutations detected are a seemingly intelligible set of letters and numbers that actually hide an easy-to-understand code language. They are: H69del / v70del, Y453F, I692V and M1229I. The first means that two amino acids, the basic units that make up the virus’s proteins (del is short for delete, in English) have been removed. The numbers identify the exact position of the protein S sequence in which it was produced. In other words, amino acids H and V (histidine and valine) were eliminated at positions 69 and 70. According to geneticist Emma Hodcroft, from the University of Bern (Switzerland), this mutation had already been observed in human coronaviruses from other countries and they seem to have no function.
The second mutation involves a replacement of Y (tyrosine) by F (phenylalanine) at position 453 of protein S. This mutation had already been seen in a person in Russia and also in coronavirus-infected minks in the Netherlands, Hodcroft explained. , who is leading a project to track different human and animal variants of the new coronavirus around the world.
Although there are still no reliable data, it is possible that this mutation is a new adaptation of the coronavirus to its new host, the mink. The mutation would allow it to better adhere and enter the cells of that animal. The coronavirus uses the same procedure to open mink cells as human cells, the ACE2 receptor. It is possible that, by pure chance, this mutation developed to better infect mink also increases the ability to bind to human cells, according to two preliminary studies that have yet to be reviewed by independent experts.
The other two mutations have not been seen before and little is known about their effects, explains Hodcroft. Probably, if they have an effect, it is not essential, especially in regards to immunity and vaccines, because, according to this geneticist, they are not in the receptor-binding domain (RBD), the part of the virus protein that is unites blocks human cells and is essential for the virus to infect.
“These mink mutations do not seem very worrisome,” explains Kirsten Lyke, a researcher at the Center for Vaccine Development at the University of Maryland (USA) and a member of the team that tests volunteers with the covid-19 vaccine developed by BioNTech and Pfizer. . Many vaccines in later stages of development, such as Oxford, Modern or this one, are based on the same strategy: introduce protein S into the patient so that their immune system learns to recognize it and neutralize it with antibodies and memory, especially the part of this protein that binds to cells, the receptor-binding domain, RBD. “The Y453F mutation was already present in some infected people, so it shouldn’t be a problem. The other three are not in the RBD and there is no data to suggest that they may decrease the effectiveness of vaccines, ”says Lyke. However, he adds, this must be confirmed in experiments that test the effectiveness against this virus, both from the plasma of people who have already had the disease and from monoclonal antibodies.
“The covid-19 vaccines were developed to generate more than one type of antibody against various parts of the S protein, so if a specific antibody does not work due to a mutation in the virus, there will be others that do,” he says. . Zhou Xing, a pathologist at McMaster University (Canada), who recently published a review of the immunizing capacity of vaccine development.
Isabel Sola, a scientist at the National Center for Biotechnology (CSIC) also warns that these mutations would only affect vaccines that are already in the manufacturing process. The rest, the ones still being tested, like Moderna, Oxford and so many others, could still slightly alter the formula to ensure that the new mutations do not affect its effectiveness. “The mutations seen in Denmark do not appear to be major changes and it would not be difficult to change vaccines to suit them,” he says.
The new coronavirus has a very slow natural mutation rate, around two per month. But things get complicated if the virus jumps between species, explains Fernando González Candelas, a professor at the University of Valencia. “One thing is the rate of mutation and another is the rate of evolution. The former is smaller than in other RNA viruses. The rate of evolution depends in part on the mutation rate, but, above all, on the action of natural selection ”, he explains. “When a host change occurs, any mutation that facilitates adaptation to the new species can be selected and, thus, a higher rate of evolution is obtained, the virus quickly adapts to the new cellular environment, the mink. The weird thing is that it maintains both abilities, easily infecting minks and humans ”, he adds.
“It is important to understand that all of this happens by chance,” says João Rodrigues, a structural biologist at Stanford University (USA), who conducted the preliminary study on the Y453F mutation. “After a long time in ‘infect humans’ mode, the virus was found among the minks. It turns out that one of the adaptations he made to this new mode of infection also works for the human mode. I don’t think this variant is more or less dangerous, but we certainly need to study it in detail. It is more concerning because it means that this variant can jump between the two species and is therefore more difficult to eradicate. In our study we say that it is now as important to limit contact between contacted humans as between infected humans and animals. Otherwise, we add more players to this evolutionary viral game ”, he highlights.
Although the threat to the vaccine is very low, the Danish authorities justify their decision. They would rather be more cautious than slip into inaction and possibly face a more serious problem in weeks or months. Farms with thousands of caged and infected minkes can act as dangerous biological incubators. “Sacrificing all the mink is very prudent and recommended,” says Margarita del Val, virologist at the CSIC. “In infected mink farms, the evolution of SARS-CoV-2 becomes more and more powerful and over time can produce variants and variants of the coronavirus that would never otherwise come out,” he explains. This is how, through recombination between species, some of the most dangerous viruses that are known appeared.
Follow coverage in real time the covid-19 crisis and follow the evolution of the pandemic in Brazil. Sign up for our newsletter daily to receive the latest news and analysis in email.
