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-first 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, and part twenty.
The near-simultaneous detection of SARS-CoV-2 variants from the four corners of the globe deepens our uncertainty regarding the future of the pandemic and our ability to control Covid-19. How serious the problem will be will depend on how many different variants there are, how they differ from one another, how capable they are of reinfecting people, and of resisting current and future vaccines. In this context, here we describe the newfound Nigerian variant (B.1.525). In an effort to discuss how variants differ from one another, this new strain helps to answer this question. It carries a variety of mutations mirroring those seen in previous dubious variants, as well as some unique to its structure. This only adds to the complexity of vaccine development in the weeks and months to come.
B.1.525 was first detected by genome sequence in mid-December in its native Nigeria but was also quickly found in cases in the United Kingdom, France, and elsewhere. After only two months, B.1.525 represented over 20% of genomes sequenced in Nigeria and was identified in around 200 cases globally. While not as prolific as some other variants, its proliferation in Nigeria may spell danger for a region of the world that has been relatively less affected than Europe or North and South America.
B.1.525’s unique mutations may increase transmissibility further still. Along the spike protein’s N-terminal domain (NTD), Q52R and A67V are located. The NTD is highly antigenic and is subject to a number of different point mutations and deletions in at least four different domains. Q52R falls outside these domains and its effects are unknown, whereas A67V falls in domain 1 and may have an effect on the NTD’s operation. We note there is another unique mutation, F888L, which we do not know the effect of at this time.
Among the point mutations and deletions in the spike protein, B.1.525 carries several which are ubiquitous in SARS-CoV-2 variants today. D614G confers increased transmissibility and is present in nearly all SARS-CoV-2 variants at this stage. Deletions 69, 70, and 144 are all found in the infamous UK variant, which also has been shown to have increased transmissibility.
E484K is also present, which is notably found in the South African and Brazilian strains is located in the receptor-binding motif and, because it is a significant change in charge from glutamine to lysine, confers approximately three-fold resistance to vaccines and tenfold resistance to convalescent antibodies. Unusually, the only other time we have seen Q677H was in two independently-derived strains in the United States.
B.1.525 also carries many mutations to the envelope, membrane, and nucleocapsid proteins, as well as ORF1ab. These are listed in the graphic below. These mutations likely increase the virus’s internal functioning capabilities, such as replication, resulting in a patient with higher viral loads in shorter times and perhaps greater sickness. More research on these mutations is needed before jumping to conclusions about the variant’s capabilities.
This variant maintains the trend we have seen in the past few months. As genome sequencing efforts increased, more new variants are discovered. With each new variant comes more nuanced mutations to its structure that aid its proliferation. Some of the mutations and variants spreading at this very moment confer vaccine-resistance.
I fear a relaxation of public health measures in reaction to vaccine distribution and recent declination in Covid-19 cases. Understandably, the ordinary person thinks themself safe after receiving their vaccine. Antibodies, however, do not last forever, and if new variants are immune-resistant, they may not even be fully effective.
This variant has all the characteristics which we associate with viruses that are more transmissible, capable of antibody resistance, and potential for increased virulence and replication. The observation that this variant has spread from West Africa to other nations around the world is yet another warning that we are likely to be inundated by a deluge of variants, not only homegrown but from all over the world. It is going to take a massive sustained effort to understand the implications of this and other variants for both the future of the pandemic and vaccine design.