The Science behind the London Christmas closure

On Saturday, Prime Minister Boris Johnson announced a very limited lockout to affect a third of England’s population, including most of south-east England and London. The lock was widely reported to be included in the New York Times, Washington Post, and Reuters.

Here I take a look at some of the science behind this decision. I have written about molecular epidemiology before. This is another example of the in-depth insights that can be provided by genomic analysis.

The main finding driving British locking appears to be the rapid increase in the number of cases represented by a specific evolutionary branch of SARS-CoV-2, the virus that causes Covid-19. The line was named B.1.1.7 by the UK Genomics Consortium COVID-19. A report published online in the blog virological.org co-authored with ten leading experts in viral evolution explains the latest findings. Highlights include:

This line has been around for a while

Patient samples in Line B.1.1.7 were first collected at the end of September.

This means that it came largely from one person. There is an interesting statement in the original blog post about this, including the idea that the new line arose in a person who was seriously ill.

There are seventeen meaningless mutations or deletions

These are the potentially important mutations. That’s a lot of changes happening all at once. For background, his RNA contains the genetic code for SARS-CoV-2. RNA is a “macromolecule” made up of nucleotides, each of which consists of a molecule of the sugar ribose, a phosphate group, and a “base” containing nitrogen. In the case of SARS-CoV-2, the genome contains a sequence of 29,881 nucleotides. This sequence of nucleotides is the plan for sequences of amino acids that are the building blocks of all the particles that go into the formation of virus grains. There is a slight loss in the genetic code so that some strains do not alter the amino acid sequence, the so-called “synergistic” mutations, and others, ie the “nonsensical” ones. Similar mutations are similar to having multiple sets of blueprints that lead to the same building. But unreasonable changes lead to real changes in the building materials. Here we have seventeen variations of the virus that all happened at the same time.

The “S” gene contains eight of these important mutations.

The S gene codes for a protein called spike. The spike protein is essential for the release of SARS-CoV-2. It is found on the surface of the virus and has a feature called a receptor binding. When the receptor binding area occurs with an enzyme, called ACE2, which is rooted in a host cell, then another enzyme, called TM serine protease 2 (TMPRSS2), releases the virus. into the cell.

Perhaps the most important of these mutations is the N501Y

The name N501Y means that mutations in the new variant cause the amino acid at site 501 to become Tyrosine (symbol Y), but earlier genotypes were coded for Asparagine (symbol N). This amino acid provides one of only six points of contact with the receptor binding domain. This means that mutation of N501Y can affect the easy entry of the virus into human cells. The N501Y mutation has been shown to experimentally cause SARS-CoV-2 to more easily attack mice. He has also appeared several independent tours, including South Africa, as explained by evolutionary physiologist Emma Hodcroft of the University of Basel.

The new line, which includes the 17 major mutations, has grown rapidly in Britain over the past six weeks.

The virological.org report only states that line B.1.1.7 “has been growing rapidly over the past 4 weeks”. However, an analysis of nextstrain.org reveals that the rise to leadership in the UK began even earlier, in late October or early November, and happened very quickly. According to the next analytical study, this mutation is now found in more than 75% of samples collected in the UK.

Line B.1.1.7 has now spread elsewhere

According to virological.org, about a third of genotypes in line B.1.1.7 from Kent (a county in England adjacent to London), one third from London, and one third from elsewhere in Britain, produce into both Scotland and Wales. In addition to this, Hodcroft reports that the web was also discovered in Denmark and Australia.

If it is in these places, it is almost certain to circulate in other parts of the unknown world.

What does this mean for Covid-19 pandemic?

The rapid expansion of the B.1.1.7 line of SARS-CoV-2 is an interesting phenomenon that needs to be explained. Most likely, it has an advantage of some sort compared to other genotypes. The fact that mutation of N501Y makes SARS-CoV-2 more potent in mice suggests that this evolutionary advantage may have something to do with the ability of the virus to take host cells, although this has not yet been established. This may be epidemiologically important, for example if the infectious dose is reduced. Similarly, there is still no evidence of effects on disease depth one way or the other.

With the close ties between the UK and many other countries, including the US, this change is expected to spread to other parts of the world. We should be vigilant.