SARS-CoV-2 is a protein virus. It appears designed to reinfect a previously inflamed host, modifying its outer layer and some of its properties. The virus is also adapting to a number of new environments, adding humans and other animals. Therefore, we will have to perceive the multifaceted nature of the adjustments it undergoes and adapt our coverage strategies, especially vaccines, to this reality. It’s not the first time humanity has faced an ever-evolving virus, as we all know with the flu.
The existing fear with SARS-CoV-2 is a new variant, BA. 2. 86, which gave the impression first in Israel, then in Denmark and more recently in the United States. We all know Omicron and how it swept the world that we had already noticed. There have been so many adjustments to Omicron’s outer spike protein that past infections have done little to protect against new infections. It remains to be determined to what extent a past infection protects against the disease.
The peak of the Omicron strain in early 2022 was BA. 2, which contained 54 amino acid mutations from the original Wuhan virus. The fear about BA. 2. 86 is that it comprises 41 amino acid mutations in addition to BA. 2 mutations, for a total of 95 mutations of the Wuhan virus. The challenge is whether or not BA. 2. 86 could be Omicron’s newest threat. Instead of waiting to see if the virus has spread globally, I analyze this virus here to summarize what it is and what is known. about its properties.
BA. 2. 86 is probably a common descendant of one of the original variants of Omicron, BA. 2, and a newer variant, XBB. In the Spike protein of BA. 2. 86, we practiced mutations of 60 amino acids, adding substitutions and deletions. Recall that the Alpha variant, which drove the second-largest wave of cases in the U. S. The U. S. Omicron (the initial wave of Omicron), contained only ten peak amino acid mutations.
We have observed many peak mutations in the worrisome variants of the past, namely K417N, N440K, S477N, N501Y, etc. However, more than a dozen mutations are unique or rare to past variants. The figures below demonstrate the significant deviation from the dominant variant. XBB. 1. 5, as well as a comparison with BA. 2 and EG. 5. 1.
In particular, the updated Covid vaccine to be rolled out this fall is designed to protect against the XBB. 1. 5 variant, but not against BA. 2. 86. The hope is that the vaccine will protect against BA. 2. 86 if widely circulated. , however, it would not be unexpected for the variant to escape booster protection, given that the degree of mutation of BA. 2. 86 at its peak is extreme.
Since the antigenicity settings are mainly, though not completely, similar to the spike protein, I’ll first talk about spike mutations in more detail. Each of the more than two dozen mutations discovered in BA. 2. 86, but not the dominant XBB. 1. 5, could give the new variant a distinct advantage, but I’ll talk about a few that I consider most remarkable.
The K356T mutation was described in the past as a mutation that could confer significant merit of immune evasion to SARS-CoV-2. The mutation adds an N-glycosylation site to the receptor-binding domain on N354, allowing for more effective antibodies. blockade. In addition, patients treated with sotrovimab were found to have developed this mutation in their Omicron infections in response, demonstrating the immune evasion and resistance of K356T.
Mutations in the N-terminal domain can cause several similar N-glycosylation sites and deserve further investigation.
In the receptor binding domain, there are several other mutations, all of which can help ACE2 binding affinity or decrease the binding efficiency of antibodies.
The P1143L mutation has been shown to potentially increase the input potency of the virus, which can be attributed to the accumulation of stability of the mutated amino acid relative to the arrangement of the spike protein.
I must draw your attention to mutations outside the Spike region, which would possibly be vital for the pathogenicity and spread of the virus. Throughout the genome, there is a wide variety of mutations in the replication-transcription complex Orf1ab (NSP1-16), some in structural proteins (E, M and N) and some in accessory proteins (Orf3a-8). The explanation why we pay attention to this is that mutations in some of those proteins, especially the N protein, can make a significant difference in the replication of the virus.
Below is the full catalog of discovered mutations of the virus.
FIGURE 4: BA. 2. 86 mutations without tips. Those in red are additional mutations discovered in the Israeli and American samples, and those in blue are additional mutations discovered in the Danish and English samples, as detailed in Figure 2.
One protein to note that is strongly mutated in BA. 2. 86 is the NSP3 protein. There are up to seven mutations in NSP3, namely T24I, V238L, G489S, N1708S, A1892T, and in some cases K1155R and T1269I. NSP3 is one of the most active proteins in the virus, playing a role in viral RNA binding, polyprotein processing, and other functions. Although the exact function of these mutations is unknown, they are more likely to increase the effectiveness of many of these mechanisms. creating a more asal and pathogenic virus.
In particular, there are already connections in all seven BA. 2. 86 cases. If we look only at the peak mutations, it can be assumed that they are the same virus, but upon closer inspection, we find that two of the cases – the Israeli and the American – involve 3 mutations discovered in the others, namely NG243S. , Orf8 T87I and S I670V.
Four other cases (three in Denmark and one in England) have a difference of their own: NSP3 K1155R. The English case has another NSP3 mutation T1269I. The most recent case detected, an American from Japan, has none of the five mutations listed. creating your own branch.
FIGURE 5: Different lineages with the BA. 2. 86 framework.
One last observation about the mutations I have to make are synonymous mutations, or those that do not cause an amino acid change. There are probably dozens of synonymous mutations scattered in the BA. 2. 86 genomes. However, collecting knowledge about those mutations is much more complex than collecting knowledge about amino acid mutations.
For example, the ends of the virus, known as the five main ends and the 3 main ends, involve those synonymous mutations, since amino acid coding does not begin until after NSP1 of the Orf1a complex. One such synonymous mutation is C241T. Along with NSP12 P323L and S D614G, C241T was part of the first set of mutations of the original wild type from Wuhan and continues to appear in all known variants of SARS-CoV-2.
Although synonymous mutations do not have an effect on the amino acid series of the virus, they do have an effect on the tertiary arrangement of the virus’s RNA, which studies have shown would possibly play a role in the adaptation of the virus to the human host environment.
For example, a recent study on the N protein of SARS-CoV-2 shows that the N-terminal domain of N recognizes and binds RNA sequences in the five major untranslated regions of the virus. The N protein is involved in RNA transcription and packaging. the genome in viral particles, a very important role in the transmission of the virus. Therefore, changing the structures of the five primary limbs could have an effect on the function and efficacy of N, which would have an effect on overall viral function from SARS-CoV-2.
As for whether BA. 2. 86 will cause a new wave of Covid cases similar to Alpha or Omicron in the coming years, I can’t say. With so few cases of BA. 2. 86 to date and so little knowledge about its pathogenicity, many questions remain.
First, is this virus transmissible and pathogenic?We know that most patients didn’t do it in a significant way, but we don’t yet know if those patients are immunocompromised, elderly, receiving chemotherapy or similar treatment. These populations are much more likely to develop serious diseases than the average healthy adult, and publishing such data may be useful in the progression of our physical fitness policy related to BA. 2. 86.
Its urgent factor is the vaccine. If the BA. 2. 86 variant took hold and created a new wave of cases, would newer vaccines be protective?This knowledge is still available. While those early detections of BA. 2. 86 are only an initial test, it remains to be seen how they will evolve in the coming weeks and months.