New York finds its personal Covid variants. The information is just not good

NEW YORK, NEW YORK – FEBRUARY 24: People wait in line to register for their vaccination appointment … [+] on February 24, 2021 at the York College Coronavirus (COVID-19) vaccination center in Jamaica in the New York borough of Queens. On February 19, Governor Andrew Cuomo announced the opening of two state-FEMA community-based locations for the coronavirus vaccine (COVID-19) in Brooklyn and Queens, and encouraged eligible individuals to get vaccinated. The sites, which are open between 8 a.m. and 8 p.m. daily, can deliver 3,000 doses per day. (Photo by Michael M. Santiago / Getty Images)

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Random variations are an essential part of all living things. It drives diversity and that is why there are so many different types. Viruses are no exception. Most viruses are experts at modifying genomes to suit their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, is not only changing, it is changing in significant ways. This is the twenty third in a series of articles on how the virus is changing and what it means for humanity. Read the rest: part one, part two, part three, part four, part five, part six, part seven, part eight, part nine, part ten, part eleven, part twelve, part thirteen, part fourteen, part fifteen, Part sixteen, part seventeen, part eighteen, part nineteen, part twenty, part twenty-one and part twenty-two.

In one type of hostile takeover, SARS-CoV-2 variants have surfaced around the world, threatening progress in ending the Covid-19 pandemic. Certain mutations give some variants the ability to evade vaccines, while others make the virus far more transmissible and deadly. Here we are analyzing the genome of another of these shady variants identified in New York (B.1.526). This strain in particular carries several known mutations that are known to be problematic and some of its own.

The variant was first identified in late November by researchers from the Department of Biology and Biotechnology at the California Institute of Technology and made up nearly 30% of the genomes sequenced from New York by mid-February 2021, as shown in the table below.

Increase in isolates containing spike mutations T95I and D253G

Increase in isolates containing spike mutations T95I and D253G

Bjorkman et al. // California Institute of Technology

Let’s give a brief overview of what we find in the New York variant, actually two variants that have a common name. The first of these, a mutation at amino acid 614 (D614G), was first identified as a minor variant in Europe in March 2020. The change in a single amino acid gave such a transfer advantage over previous stains as originally found in Wuhan, China. Today it is ubiquitous and is found in almost every SARS-CoV-2 isolate in the world. This single amino acid change improves the stability of the spike protein on the surface of the virus. It allows the virus to more easily attach to the ACE2 receptor surface to begin the infection process. This small change allowed the viruses that carried it to outperform all others. Today we are facing many similar changes, each with a big or small benefit that will allow a virus to better adapt to an ever-changing environment as we aim to try to mitigate its havoc through behavior changes and medication.

Some of the B.1.526 variants carry a mutation at position 484 (E484K). This is one of the most significant mutations as we know what the virus can do with it. The same change is present in several other problematic variants, including those that were first isolated in South Africa and Brazil. Viruses that carry the E484K (sometimes called the EEEK! Mutation) are less sensitive to protective antibodies that are produced in response to natural infection or vaccination. In practice, this means that these viruses can re-infect viruses that have already been infected. It also means that the current generation of vaccines are less effective at protecting people who encounter the virus.

The B.1.526 variants that lack the E484K change have another at position 477 (S477N). This mutation also occurs in the region of the virus that binds the ACE2 receptor. We have a clue how it can help the virus spread quickly. Laboratory experiments show that this change dramatically increases the binding of the virus to the receptor, a trait we know from the success of the D614G variant, which gives the virus a competitive advantage. For us, this means that variants of B1.526 that carry this change are more contagious.

Both B.1.526 variants contain a further mutation at position 701 (A701V). Before the virus can start infection, the membranes surrounding the virus and the cell must fuse. The fusion requires that the region of the spike protein that is buried deep in the structure be exposed. The mutation at 701 allows this to be done more easily and again improves the ease with which the virus can enter a target cell. This is another way for this virus to become more contagious. The New York variant developed two of the tricks of the South African variant B.1.351 independently of one another, as it also carries identical mutations at positions 484 and 701.

We know a little more about one of the other mutations that are common to the B.1.526 variants. The change at position 253 (D253G) is in a region of the spike protein called the N-terminal domain (NTD). This region is strongly antigenic, which means that the target of many antibodies is partially protective. The D253G modification protects the virus from protective antibodies and thus supports immune evasion. Combined, these changes present a malleable challenge to both the prevention of infection through standard public health measures and the current generation of vaccines.

The figure here shows the position of the B.1.526 mutations along the length of the spike protein. The spike protein folds into a complex structure. The location of each amino acid change is also shown in the composite top. The RBD indicates the region of the tip that binds to the receptor. Both the 484 and 477 variants are clearly located in the receptor binding domain. The 701 mutation is located in the spike strain next to the region required for membrane fusion.

Mutations to the spike protein

Mutations to the spike protein

Visual representation of B.1.526 point mutations

Visual representation of B.1.526 point mutations

Bjorkman et al. // California Institute of Technology

The New York variants also share other mutations that are scattered throughout the genome, as shown below, as do several rapidly spreading variants. Much more research is needed before we understand how or if these mutations affect transmission, immune evasion, and virulence.

Mutations outside of the spike protein

Mutations outside of the spike protein

It is remarkable how quickly the B.1.526 variants emerged as the dominant strains in the New York area in the late weeks of February. You have a competitive advantage over others in spreading from person to person. The identity of mutations in these variants with the known risk of infection, immune resistance and virulence should keep us all on our guard. The news is a cruel blow to us, who had hoped to relax harm control measures and enjoy our newfound vaccine protection.

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