New York Finds Its Own Covid Variants. The News Is Not Good.

(Posted on Friday, February 26, 2021)

Random variation is an essential component of all living things. It drives diversity, and it is why there are so many different species. Viruses are no exception. Most viruses are experts at changing genomes to adapt to their environment. We now have evidence that the virus that causes Covid, SARS-CoV-2, not only changes but changes in ways that are significant. This is the twenty-third part of a series of articles on how the virus changes and what that 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 a hostile takeover of sorts, SARS-CoV-2 variants have emerged the world over, threatening progress made towards ending the Covid-19 pandemic. Certain mutations confer some variants the ability to evade vaccines, whereas others make the virus far more transmissible and more deadly. Here, we analyze the genetic makeup of another one of these shifty variants identified in New York (B.1.526). This strain, in particular, carries several well know mutations known to be troublesome and some of its very own.

The variant was first identified in late November by researchers at the California Institute of Technology Biology and Biological Engineering Division grew to account for nearly 30% of genomes sequenced from New York through mid-February 2021, as shown in the table below.

Let’s take a brief tour of what we find in the New York variant, actually two variants sharing a common designation.  The first of these, a mutation at amino acid 614 (D614G), was first noticed in March 2020 in Europe as a minor variant. The change in a single amino acid conferred such an advantage in transmission over earlier stains, such as that found initially 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 bind to the ACE2 receptor surface more readily to begin the process of infection.  That small change allowed the viruses that carried it to outcompete all others. Today, we face many similar changes, each of which confers some advantage, large or small, that allows one virus to adapt better to an ever-changing environment as we, its target, seek to moderate its ravages through behavior change and medicine.

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 some of what it allows the virus to do. The same change is present in several other troublesome variants, including those first isolated in South Africa and Brazil. Viruses which carry the E484K (sometimes called the EEEK! mutation) are less sensitive to protective antibodies made in response to natural infection or vaccination. In practical terms, that means that these viruses can reinfect those already infected. It also means that the current generation of vaccines is less effective in 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 some inkling of how it may help the virus spread rapidly. Laboratory experiments show that this change dramatically increases how tightly the virus can bind to the receptor, a feature we know from the success of the D614G variant that gives the virus a competitive advantage. For us, this means that variants of B1.526 that carry this change are more contagious.

Both of the B.1.526 variants contain another mutation at position 701 (A701V).  Before the virus can begin infection, the membranes surrounding the virus and cell must fuse. Fusion requires that the region of the spike protein buried deep in the structure be free. The mutation at 701 allows that to happen more easily, once again improving the ease with which the virus can enter a target cell. That is yet another way for this virus to become more contagious.  The New York variant has independently evolved two of the tricks used by the South African variant B.1.351 as it too carries identical mutations at positions 484 and 701.

We know something more about one of the other mutations 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 highly antigenic, meaning that is the target of many antibodies is partially protective. The D253G change shields the virus from protective antibodies, assisting immune evasion. When combined, these changes present a formable challenge both to the prevention of infection by standard public health measures and the current generation of vaccines.

The figure here depicts the location 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 assembled spike. The RBD indicates the region of the spike that binds to the receptor. Both the 484 and 477 variants clearly reside in the receptor-binding domain. The 701 mutation is located in the spike stem adjacent to the region necessary for membrane fusion.

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

It is striking how rapidly the B.1.526 variants have emerged as dominant strains in the New York area in the late weeks of February. They have a competitive advantage over others in the spread from person to person. The identity of mutations in these variants with that known pose increased risks contagion, immune resistance, and virulence should put us all on guard. The news comes as a cruel blow to this of us who were hoping to be able to relax mitigation measures and revel in our newfound vaccine-induced protection.

Read the full article on Forbes.

Originally published on February 26, 2021.