B.1.1.7 coronavirus variant takes on a worrying new mutation

Cartoon representation of coronaviruses.

As the world runs to get vaccinations in the weapon, one of the most concerned coronavirus variants seems to be getting a little more worrying.

Researchers in the UK have identified at least 15 cases of B.1.1.7 variants that contain an additional mutation: E484K, a mutation that has been seen in others with respect to variants and one that may make current vaccines less effective at to prevent infection. The B.1.1.7 variant, first identified in the UK, is known to spread more easily among humans than earlier strains of the pandemic coronavirus SARS-CoV-2. And according to some preliminary evidence, it can cause worse diseases.

So far, B.1.1.7 variants with E484K seem rare. On Monday, Public Health England reported in a technical briefing that the E484K was detected in only 11 B.1.1.7 variants among more than 200,000 virus tests. For now, it is unclear whether the supplemented mutants will rise and become dominant in the population or spread. It is also not entirely clear what the addition of E484K for B.1.1.7 means in humans. Preliminary laboratory experiments suggest that the mutation alone, and its presence in B.1.1.7 specifically, may help the virus to evade immune responses. But more studies and clinical data are needed to understand the full effect of the new additive.

However, the new mutation in B.1.1.7 undoubtedly again indicates that the pandemic coronavirus is not ready to try to outwit us, even though numerous vaccines prove that it can prevent infection and prevent serious diseases. As long as we continue to spread the virus among us, the virus will have ample opportunity to hone its disease-causing and vaccine-evoking capabilities – and it will use it. The findings emphasize once again that we must continue to use proven mitigation efforts – physical distance, mask wear, hand hygiene, good ventilation and the avoidance of crowds and enclosed areas – to reduce transmission as much as possible while vaccination efforts are in progress.

Given the current state of the pandemic and what we already know about the virus, some researchers say that finding E484K in B.1.1.7 is not surprising at all. It may have been just a matter of time.

Variant

B.1.1.7 made headlines worldwide in early December after researchers in the UK saw over a matter of a few weeks thereafter how larger and larger volumes of cases there were. Further data and analyzes support the initial fear that it seems to spread more easily between people. Although research continues, some estimates suggest that it is approximately 50 percent more transmissible than previous SARS-CoV-2 strains. It has since been found in more than 70 countries, including the United States. The U.S. Centers for Disease Control and Prevention estimates that B.1.1.7 could become the dominant tribe in the country in March.

The rapidly spreading variant was first found with 23 mutations, with three of particular concern. The three contain a vein protein of the virus, the characteristic club-like proteins that push out of the spherical particle of the virus. The virus uses its nails to attach to and enter cells, causing an infection. It is suspected that at least two of B.1.1.7’s peak mutations, including the infamous N501Y, could more easily enter the virus into cells.

While B.1.1.7 invaded the United Kingdom, there were two other variants in the Southern Hemisphere: the 501Y.V2 / B.1.351 variant identified in South Africa and the P.1 variant identified in Brazil is. Both variants are feared to evade immune responses following infections with earlier strains of the virus or from current vaccines, meaning that people vaccinated or recovered from COVID-19 may still be vulnerable to infection by the variants. And both variants contain the E484K mutation in their ear protein.

The mutation is located in a critical area of ​​the peak, called the receptor binding domain, or RBD. The RBD is the area of ​​the peak that – as the name implies – binds directly to a protein receptor on human cells called ACE2. Spike’s RBD binding to ACE2 is the cause of an infection. With such a key role, the RBD is a primary target for the strongest antibodies, called neutralizing antibodies. If an antibody gets stuck on the RBD, it can prevent the virus from binding to ACE2 and infecting cells. Conversely, mutations can shed antibodies to the RBD, which in turn depletes potentially powerful immune responses.

Mutation mashup

Preliminary laboratory studies have suggested that mutations to the RBD’s protein code at amino acid position 484 were best at evading antibodies from people recovering from COVID-19. The specific mutation E484K – to change a glutamic acid (E) at position 484 into lysine (K) – reduced the potency of antibodies ten times. Researchers saw similar drops in potency neutralization when they set up E484K additive peak proteins against antibodies from humans vaccinated with one of the two mRNA vaccines currently approved in the United States (Moderna and Pfizer / BioNTech vaccines ).

Similarly, some very preliminary data – from a not yet peer-reviewed study with significant caveats – indicate that the addition of the E484K mutation to B.1.1.7’s ear protein may mean that current vaccines will be less effective. The study used the use of antibody products obtained from humans, which gave only the first dose of the Pfizer / BioNTech mRNA vaccine. As before, the presence of E484K meant that it required much higher antibody levels to neutralize the virus. However, it is important to note that antibody levels will be higher after the second dose of the vaccine.

The good news in all of this is that both mRNA vaccines are very effective (about 95 percent) in preventing COVID-19. Even with the reduction in the efficacy of cunning variants, experts expect that the vaccines will continue to be protective, especially against serious diseases. But the fact that E484K has now emerged in each of the three coronavirus variants suggests that the mutation offers some benefit. And the virus is going to keep such benefits, as long as we let it spread.

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