Inside the B.1.1.7 Coronavirus Variant - The New York Times

These genetic instructions force infected human cells to assemble up to 29 kinds of proteins that help the coronavirus multiply and spread.

As viruses replicate, small copying errors known as mutations naturally arise in their genomes.

A lineage of coronaviruses will typically accumulate one or two random mutations each month.

Some mutations have no effect on the coronavirus proteins made by the infected cell.

Other mutations might alter a protein’s shape by changing or deleting one of its amino acids, the building blocks that link together to form the protein.

A coronavirus variant first reported in Britain has 17 recent mutations that change or delete amino acids in viral proteins.

The variant was named Variant of Concern 202012/01 by Public Health England, and is part of the B.1.1.7 lineage of coronaviruses.

Amino acid.

Amino acid.

AMINO ACID.

Amino acid.

Amino acid.

AMINO ACID.

Amino acid.

Amino acid.

AMINO ACID

Notable mutations in the B.1.1.7 lineage are listed below

Six other mutations, not shown in the diagram above, do not change an amino acid

Researchers are most concerned about the eight B.1.1.7 mutations that change the shape of the coronavirus spike, which the virus uses to attach to cells and slip inside

Each spike is a group of three intertwined proteins:

Building one of these spike proteins typically takes 1,273 amino acids, which can be written as letters:

Spike proteins in the B.1.1.7 lineage have two deletions and six substitutions in this sequence of amino acids

Written as letters, a B.1.1.7 spike protein looks like this:

These mutations alter the shape of the spike protein by changing how the amino acids fold together into a complex shape

Scientists suspect that one mutation, called N501Y, is very important in making B.1.1.7 coronaviruses more contagious

The mutation’s name refers to the nature of its change: the 501st amino acid in the spike protein switched from N (asparagine) to Y (tyrosine)

The N501Y mutation changes an amino acid near the top of each spike protein, where it makes contact with a special receptor on human cells

Location of the N501Y mutation

on one of the three spike proteins

Location of the N501Y mutation

on one of the three spike proteins

Because spike proteins form sets of three, the mutation appears in three places on the spike tip:

Top view of the coronavirus spike,

showing the N501Y mutations

Top view of the coronavirus spike,

showing the N501Y mutations

In a typical coronavirus, the tip of the spike protein is like an ill-fitting puzzle piece

The N501Y mutation seems to refine the shape of the puzzle piece, allowing a tighter fit and increasing the chance of a successful infection

Researchers think the N501Y mutation has evolved independently in many different coronavirus lineages

In addition to the B.1.1.7 lineage, it has been identified in variants from Australia, Brazil, Denmark, Japan, the Netherlands, South Africa, Wales, Illinois, Louisiana, Ohio and Texas

In addition to N501Y, the B.1.1.7 has 16 other mutations that might benefit the virus in other ways

It’s also possible that they might be neutral mutations, which have no effect one way or the other

One mysterious mutation in the B.1.1.7 lineage deletes the 69th and 70th amino acids in the spike protein

It’s possible that it changes the shape of the spike protein in a way that makes it harder for antibodies to attach

In another recurrent deletion region, a number of coronavirus lineages are missing either the 144th or 145th amino acid in the spike protein

The name of the mutation comes from the two tyrosines (Y) that are normally in those positions in the protein

This mutation changes an amino acid from P to H on the stem of the coronavirus spike:

When spike proteins are assembled on the surface of a coronavirus, they’re not yet ready to attach to a cell

Like N501Y, the P681H mutation has arisen in other coronavirus lineages besides B.1.1.7

But it’s rare for one lineage to carry both mutations

R52I mutation

In one experiment, scientists deleted the protein and found that the coronavirus could still spread

ORF8 is typically only 121 amino acids long:

But a B.1.1.7 mutation changes the 27th amino acid from Q to a genetic Stop sign:

When the infected cell builds the ORF8 protein, it stops at this mutation and leaves a stump only 26 amino acids long:

But if losing the protein leaves B.1.1.7 at a disadvantage, it’s possible that the advantages of another mutation like N501Y might make up for the loss

Two other B.1.1.7 mutations appear in ORF8 after the stop point, changing R to I and Y to C:

Q27stop mutation

R52I mutation

Because the ORF8 protein is cut short, these two mutations may do nothing

The B.1.1.7 lineage has now been detected in over 50 countries, including the United States

B.1.1.7 lineage

A number of researchers suspect that B.1.1.7 gained many of its mutations within a single person

When these patients are treated with convalescent plasma, which contains coronavirus antibodies, natural selection may favor viruses with mutations that let them escape the attack

Once the B.1.1.7 lineage evolved its battery of mutations, it may have been able to spread faster from person to person

In many countries, the D614G lineage came to dominate the population of coronaviruses

B.1.1.7 descends from the D614G lineage

D614G mutation

This variant has eight mutations that change amino acids in the spike protein

Among these mutations is N501Y, which helps the spike latch on more tightly to human cells

L18F mutation

N501Y mutation

Antibodies generated by the Pfizer-BioNTech vaccine were able to lock on to coronavirus spikes that have the N501Y spike mutation, preventing the virus from infecting cells in the lab